View source for B cell

{{Short description|Type of white blood cell}}
{{About|the immune system cell|the electrical cell|Battery (vacuum tube)|β-cell of pancreas|beta cell}}
{{Infobox cell
| Name        = B  lymphocyte
cell
| Latin       = lymphocytus B
| Image       = Blausen 0624 Lymphocyte B cell (crop).png
| Caption     = Animation of B cell
| Precursor   = [[Hematopoietic stem cell]]
| System      = [[Immune system]]
}}

'''B cells''', also known as '''B lymphocytes''', are a type of [[lymphocyte]].<ref name=":0">{{Cite book|title = Janeway's Immunobiology |edition=8th | vauthors = Murphy K |publisher = Garland Science |year = 2012|isbn = 978-0-8153-4243-4|location = New York}}</ref> They function in the [[humoral immunity]] component of the [[adaptive immune system]].<ref name=":0" /> B cells produce [[antibody]] molecules which may be either secreted or inserted into the plasma membrane where they serve as a part of [[B-cell receptor]]s.<ref name="Alberts 2002">{{Cite book | vauthors = Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P |date=2002| chapter = B Cells and Antibodies | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK26884/| title = Molecular Biology of the Cell |publisher=Garland Science | edition = 4th }}</ref> When a naïve or [[memory B cell]] is activated by an antigen, it proliferates and differentiates into an antibody-secreting effector cell, known as a plasmablast or plasma cell.<ref name="Alberts 2002"/> In addition, B cells [[Antigen presentation|present antigens]] (they are also classified as professional [[Antigen-presenting cell|antigen-presenting cells, APCs]]) and secrete [[cytokine]]s.<ref name=":0" /> In [[mammal]]s B cells [[Cellular differentiation|mature]] in the [[bone marrow]], which is at the core of most [[bone]]s.<ref name=":1">{{cite journal | vauthors = Cooper MD | title = The early history of B cells | journal = Nature Reviews. Immunology | volume = 15 | issue = 3 | pages = 191–197 | date = March 2015 | pmid = 25656707 | doi = 10.1038/nri3801 | author-link = Max Dale Cooper | doi-access = free }}</ref> In [[bird]]s, B cells mature in the [[bursa of Fabricius]], a lymphoid organ where they were first discovered by Chang and Glick,<ref>{{Cite journal |last1=Glick |first1=Bruce |last2=Chang |first2=Timothy S. |last3=Jaap |first3=R. George |date=1956-01-01 |title=The Bursa of Fabricius and Antibody Production |journal=Poultry Science |language=en |volume=35 |issue=1 |pages=224–225 |doi=10.3382/ps.0350224 |issn=0032-5791|doi-access=free }}</ref> which is why the ''B'' stands for ''bursa'' and not ''bone marrow'', as commonly believed.

B cells, unlike the other two classes of lymphocytes, [[T cell]]s and [[natural killer cell]]s, express [[B-cell receptor|B cell receptors (BCRs)]] on their [[cell membrane]].<ref name=":0" /> BCRs allow the B cell to [[Molecular binding|bind]] to a foreign [[antigen]], against which it will initiate an antibody response.<ref name=":0" /> B cell receptors are extremely specific, with all BCRs on a B cell recognizing the same [[epitope]].<ref>{{cite journal |last1=Jespersen |first1=Martin Closter |last2=Mahajan |first2=Swapnil |last3=Peters |first3=Bjoern |last4=Nielsen |first4=Morten |last5=Marcatili |first5=Paolo |title=Antibody Specific B-Cell Epitope Predictions: Leveraging Information From Antibody-Antigen Protein Complexes |journal=Frontiers in Immunology |doi=10.3389/fimmu.2019.00298 |date=2019|volume=10 |article-number=298 |pmid=30863406 |pmc=6399414 |doi-access=free }}</ref>

==Development==
[[File:Early B cell development.jpg|thumb|left|Early B cell development: from stem cell to immature B cell]]
[[File:Transitional B cell development.PNG|thumb|[[Transitional B cell]] development: from immature B cell to MZ B cell or mature (FO) B cell]]

B cells develop from [[Hematopoietic stem cell|hematopoietic stem cells (HSCs)]] that originate from [[bone marrow]].<ref name="BCDTfBcells">{{cite journal | vauthors = Fischer U, Yang JJ, Ikawa T, Hein D, Vicente-Dueñas C, Borkhardt A, Sánchez-García I | title = Cell Fate Decisions: The Role of Transcription Factors in Early B-cell Development and Leukemia | journal = Blood Cancer Discovery | volume = 1 | issue = 3 | pages = 224–233 | date = November 2020 | pmid = 33392513 | pmc = 7774874 | doi = 10.1158/2643-3230.BCD-20-0011 | doi-access = free }}</ref><ref name=":2">{{cite journal | vauthors = Kondo M | title = Lymphoid and myeloid lineage commitment in multipotent hematopoietic progenitors | journal = Immunological Reviews | volume = 238 | issue = 1 | pages = 37–46 | date = November 2010 | pmid = 20969583 | pmc = 2975965 | doi = 10.1111/j.1600-065X.2010.00963.x }}</ref> HSCs first differentiate into [[multipotent progenitor]] (MPP) cells, then [[common lymphoid progenitor]] (CLP) cells.<ref name=":2" /> From here, their development into B cells occurs in several stages (shown in image to the right), each marked by various [[gene expression]] patterns and [[Antibody|immunoglobulin]] [[Immunoglobulin heavy chain|H chain]] and [[Immunoglobulin light chain|L chain]] [[Locus (genetics)|gene loci]] arrangements, the latter due to B cells undergoing [[V(D)J recombination]] as they develop.<ref name=":3">{{cite journal | vauthors = Pelanda R, Torres RM | title = Central B-cell tolerance: where selection begins | journal = Cold Spring Harbor Perspectives in Biology | volume = 4 | issue = 4 | article-number = a007146 | date = April 2012 | pmid = 22378602 | pmc = 3312675 | doi = 10.1101/cshperspect.a007146 }}</ref>

B cells undergo two types of selection while developing in the bone marrow to ensure proper development, both involving B cell receptors (BCR) on the surface of the cell. Positive selection occurs through antigen-independent signalling involving both the pre-BCR and the BCR.<ref name=":4">{{cite journal | vauthors = Mårtensson IL, Almqvist N, Grimsholm O, Bernardi AI | title = The pre-B cell receptor checkpoint | journal = FEBS Letters | volume = 584 | issue = 12 | pages = 2572–2579 | date = June 2010 | pmid = 20420836 | doi = 10.1016/j.febslet.2010.04.057 | bibcode = 2010FEBSL.584.2572M | s2cid = 43158480 | doi-access = free }}</ref><ref name=":5">{{cite journal | vauthors = LeBien TW, Tedder TF | title = B lymphocytes: how they develop and function | journal = Blood | volume = 112 | issue = 5 | pages = 1570–1580 | date = September 2008 | pmid = 18725575 | pmc = 2518873 | doi = 10.1182/blood-2008-02-078071 }}</ref> If these receptors do not bind to their [[Ligand (biochemistry)|ligand]], B cells do not receive the proper signals and cease to develop.<ref name=":4" /><ref name=":5" /> Negative selection occurs through the binding of self-antigen with the BCR; if the BCR can bind strongly to self-antigen, then the B cell undergoes one of four fates: [[clonal deletion]], [[receptor editing]], [[Clonal anergy|anergy]], or ignorance (B cell ignores signal and continues development).<ref name=":5" /> This negative selection process leads to a state of [[central tolerance]], in which the mature B cells do not bind self antigens present in the bone marrow.<ref name=":3" />

To complete development, immature B cells migrate from the bone marrow into the spleen as [[transitional B cells]], passing through two transitional stages: T1 and T2.<ref>{{cite journal | vauthors = Loder F, Mutschler B, Ray RJ, Paige CJ, Sideras P, Torres R, Lamers MC, Carsetti R | display-authors = 6 | title = B cell development in the spleen takes place in discrete steps and is determined by the quality of B cell receptor-derived signals | journal = The Journal of Experimental Medicine | volume = 190 | issue = 1 | pages = 75–89 | date = July 1999 | pmid = 10429672 | pmc = 2195560 | doi = 10.1084/jem.190.1.75 }}</ref> Throughout their migration to the spleen and after spleen entry, they are considered T1 B cells.<ref name=":6">{{cite journal | vauthors = Chung JB, Silverman M, Monroe JG | title = Transitional B cells: step by step towards immune competence | journal = Trends in Immunology | volume = 24 | issue = 6 | pages = 343–349 | date = June 2003 | pmid = 12810111 | doi = 10.1016/S1471-4906(03)00119-4 }}</ref> Within the spleen, T1 B cells transition to T2 B cells.<ref name=":6" /> T2 B cells differentiate into either follicular (FO) B cells or marginal zone (MZ) B cells depending on signals received through the BCR and other receptors.<ref>{{cite journal | vauthors = Cerutti A, Cols M, Puga I | title = Marginal zone B cells: virtues of innate-like antibody-producing lymphocytes | journal = Nature Reviews. Immunology | volume = 13 | issue = 2 | pages = 118–132 | date = February 2013 | pmid = 23348416 | pmc = 3652659 | doi = 10.1038/nri3383 }}</ref> Once differentiated, they are now considered mature B cells, or naïve B cells.<ref name=":6" />

==Activation==
[[File:B cell activation naive to plasma cell.png|thumb|left|B cell activation: from immature B cell to plasma cell or memory B cell]]
[[File:B cell function.png|thumb|Basic B cell function: bind to an antigen, receive help from a cognate helper T cell, and differentiate into a [[plasma cell]] that secretes large numbers of antibodies]]

B cell activation occurs in the [[secondary lymphoid organs]] (SLOs), such as the [[spleen]] and [[lymph nodes]].<ref name=":0" /> After B cells mature in the bone marrow, they migrate through the blood to SLOs, which receive a constant supply of antigen through circulating [[lymph]].<ref>{{cite journal | vauthors = Harwood NE, Batista FD | title = Early events in B cell activation | journal = Annual Review of Immunology | volume = 28 | issue = 1 | pages = 185–210 | date = 2010-01-01 | pmid = 20192804 | doi = 10.1146/annurev-immunol-030409-101216 }}</ref> At the SLO, B cell activation begins when the B cell binds to an antigen via its BCR.<ref name=":7">{{cite journal | vauthors = Yuseff MI, Pierobon P, Reversat A, Lennon-Duménil AM | title = How B cells capture, process and present antigens: a crucial role for cell polarity | journal = Nature Reviews. Immunology | volume = 13 | issue = 7 | pages = 475–486 | date = July 2013 | pmid = 23797063 | doi = 10.1038/nri3469 | s2cid = 24791216 }}</ref>  Although the events taking place immediately after activation have yet to be completely determined, it is believed that B cells are activated in accordance with the kinetic segregation model {{Citation needed|reason = the mechanism of activation is actually quite controversial|date=April 2019}}, initially determined in T lymphocytes. This model denotes that before antigen stimulation, receptors diffuse through the membrane coming into contact with [[Lck]] and [[CD45]] in equal frequency, rendering a net equilibrium of phosphorylation and non-phosphorylation. It is only when the cell comes in contact with an antigen presenting cell that the larger CD45 is displaced due to the close distance between the two membranes. This allows for net phosphorylation of the BCR and the initiation of the signal transduction pathway{{Citation needed|date=April 2019}}. Of the three B cell subsets, FO B cells preferentially undergo T cell-dependent activation while MZ B cells and B1 B cells preferentially undergo T cell-independent activation.<ref name=":8">{{cite journal | vauthors = Nutt SL, Hodgkin PD, Tarlinton DM, Corcoran LM | title = The generation of antibody-secreting plasma cells | journal = Nature Reviews. Immunology | volume = 15 | issue = 3 | pages = 160–171 | date = March 2015 | pmid = 25698678 | doi = 10.1038/nri3795 | s2cid = 9769697 }}</ref>

B cell activation is enhanced through the activity of [[Complement receptor 2|CD21]], a surface receptor in complex with surface proteins [[CD19]] and [[CD81]] (all three are collectively known as the B cell coreceptor complex).<ref>{{cite journal | vauthors = Asokan R, Banda NK, Szakonyi G, Chen XS, Holers VM | title = Human complement receptor 2 (CR2/CD21) as a receptor for DNA: implications for its roles in the immune response and the pathogenesis of systemic lupus erythematosus (SLE) | journal = Molecular Immunology | volume = 53 | issue = 1–2 | pages = 99–110 | date = January 2013 | pmid = 22885687 | pmc = 3439536 | doi = 10.1016/j.molimm.2012.07.002 }}</ref> When a BCR binds an antigen tagged with a fragment of the C3 complement protein, CD21 binds the C3 fragment, co-ligates with the bound BCR, and signals are transduced through CD19 and CD81 to lower the activation threshold of the cell.<ref>{{cite journal | vauthors = Zabel MD, Weis JH | title = Cell-specific regulation of the CD21 gene | journal = International Immunopharmacology | volume = 1 | issue = 3 | pages = 483–493 | date = March 2001 | pmid = 11367532 | doi = 10.1016/S1567-5769(00)00046-1 | series = Unraveling Mechanisms and Discovering Novel Roles for Complement }}</ref>

===T cell-dependent activation===
Antigens that activate B cells with the help of T-cell are known as T cell-dependent (TD) antigens and include foreign proteins.<ref name=":0" /> They are named as such because they are unable to induce a humoral response in organisms that lack T cells.<ref name=":0" /> B cell responses to these antigens takes multiple days, though antibodies generated have a higher affinity and are more functionally versatile than those generated from T cell-independent activation.<ref name=":0" />

Once a BCR binds a TD antigen, the antigen is taken up into the B cell through [[receptor-mediated endocytosis]], [[Proteolysis|degraded]], and presented to T cells as peptide pieces in complex with [[MHC class II|MHC-II molecules]] on the cell membrane.<ref>{{cite journal | vauthors = Blum JS, Wearsch PA, Cresswell P | title = Pathways of antigen processing | journal = Annual Review of Immunology | volume = 31 | issue = 1 | pages = 443–473 | date = 2013-01-01 | pmid = 23298205 | pmc = 4026165 | doi = 10.1146/annurev-immunol-032712-095910 }}</ref> [[T helper cell|T helper (T<sub>H</sub>) cells]], typically [[Follicular B helper T cells|follicular T helper (T<sub>FH</sub>) cells]] recognize and bind these MHC-II-peptide complexes through their [[T cell receptor|T cell receptor (TCR)]].<ref name=":9">{{cite journal | vauthors = Crotty S | title = A brief history of T cell help to B cells | journal = Nature Reviews. Immunology | volume = 15 | issue = 3 | pages = 185–189 | date = March 2015 | pmid = 25677493 | pmc = 4414089 | doi = 10.1038/nri3803 }}</ref> Following TCR-MHC-II-peptide binding, T cells express the surface protein [[CD154|CD40L]] as well as cytokines such as [[Interleukin 4|IL-4]] and [[Interleukin 21|IL-21]].<ref name=":9" /> CD40L serves as a necessary co-stimulatory factor for B cell activation by binding the B cell surface receptor [[CD40 (protein)|CD40]], which promotes B cell [[Cell growth|proliferation]], [[immunoglobulin class switching]], and [[somatic hypermutation]] as well as sustains T cell growth and differentiation.<ref name=":0" /> T cell-derived cytokines bound by B cell [[cytokine receptor]]s also promote B cell proliferation, immunoglobulin class switching, and somatic hypermutation as well as guide differentiation.<ref name=":9" /> After B cells receive these signals, they are considered activated.<ref name=":9" /> [[File:T-dependent B cell activation.png|thumb|T-dependent B cell activation]]

Once activated, B cells participate in a two-step differentiation process that yields both short-lived plasmablasts for immediate protection and [[long-lived plasma cell]]s and memory B cells for persistent protection.<ref name=":8" /> The first step, known as the extrafollicular response, occurs outside lymphoid follicles but still in the SLO.<ref name=":8" /> During this step activated B cells proliferate, may undergo immunoglobulin class switching, and differentiate into plasmablasts that produce early, weak antibodies mostly of class IgM.<ref>{{cite journal | vauthors = MacLennan IC, Toellner KM, Cunningham AF, Serre K, Sze DM, Zúñiga E, Cook MC, Vinuesa CG | display-authors = 6 | title = Extrafollicular antibody responses | journal = Immunological Reviews | volume = 194 | pages = 8–18 | date = August 2003 | pmid = 12846803 | doi = 10.1034/j.1600-065x.2003.00058.x | s2cid = 2455541 }}</ref>
[[File:Dark, light, mantle and marginal zones of a secondary follicle.png|thumb|Histology of a normal [[lymphoid follicle]], with germinal center in the middle.]]
The second step consists of activated B cells entering a lymphoid follicle and forming a [[Germinal center|germinal center (GC)]], which is a specialized microenvironment where B cells undergo extensive proliferation, immunoglobulin class switching, and [[affinity maturation]] directed by somatic hypermutation.<ref name=":10">{{cite journal | vauthors = Shlomchik MJ, Weisel F | title = Germinal center selection and the development of memory B and plasma cells | journal = Immunological Reviews | volume = 247 | issue = 1 | pages = 52–63 | date = May 2012 | pmid = 22500831 | doi = 10.1111/j.1600-065X.2012.01124.x | s2cid = 5362003 | url = https://zenodo.org/record/1064236 }}</ref> These processes are facilitated by T<sub>FH</sub>  and follicular dendritic cells within the GC and generate both high-affinity memory B cells and long-lived plasma cells.<ref name=":8" /><ref>{{Cite journal |last1=Heesters |first1=Balthasar A. |last2=Chatterjee |first2=Priyadarshini |last3=Kim |first3=Young-A. |last4=Gonzalez |first4=Santiago F. |last5=Kuligowski |first5=Michael P. |last6=Kirchhausen |first6=Tomas |last7=Carroll |first7=Michael C. |date=2013-06-27 |title=Endocytosis and Recycling of Immune Complexes by Follicular Dendritic Cells Enhances B Cell Antigen Binding and Activation |journal=Immunity |volume=38 |issue=6 |pages=1164–1175 |doi=10.1016/j.immuni.2013.02.023 |pmid=23770227 |issn=1074-7613|pmc=3773956 }}</ref> Resultant plasma cells secrete large numbers of antibodies and either stay within the SLO or, more preferentially, migrate to bone marrow.<ref name=":10" />

===T cell-independent activation===
{{Main|T independent antigen (TI)}}
Antigens that activate B cells without T cell help are known as [[T independent antigen (TI)|T cell-independent (TI) antigens]]<ref name=":0" /> and include foreign polysaccharides and unmethylated CpG DNA.<ref name=":8" /> They are named as such because they are able to induce a humoral response in organisms that lack T cells.<ref name=":0" /> B cell response to these antigens is rapid, though antibodies generated tend to have lower affinity and are less functionally versatile than those generated from T cell-dependent activation.<ref name=":0" />

As with TD antigens, B cells activated by TI antigens need additional signals to complete activation, but instead of receiving them from T cells, they are provided either by recognition and binding of a common microbial constituent to [[Toll-like receptor|toll-like receptors (TLRs)]] or by extensive crosslinking of BCRs to repeated epitopes on a bacterial cell.<ref name=":0" /> B cells activated by TI antigens go on to proliferate outside lymphoid follicles but still in SLOs (GCs do not form), possibly undergo immunoglobulin class switching, and differentiate into short-lived plasmablasts that produce early, weak antibodies mostly of class IgM, but also some populations of long-lived plasma cells.<ref name=":11">{{cite journal | vauthors = Bortnick A, Chernova I, Quinn WJ, Mugnier M, Cancro MP, Allman D | title = Long-lived bone marrow plasma cells are induced early in response to T cell-independent or T cell-dependent antigens | journal = Journal of Immunology | volume = 188 | issue = 11 | pages = 5389–5396 | date = June 2012 | pmid = 22529295 | pmc = 4341991 | doi = 10.4049/jimmunol.1102808 }}</ref>

=== Memory B cell activation ===
Memory B cell activation begins with the detection and binding of their target antigen, which is shared by their parent B cell.<ref name=":13">{{cite journal | vauthors = McHeyzer-Williams M, Okitsu S, Wang N, McHeyzer-Williams L | title = Molecular programming of B cell memory | journal = Nature Reviews. Immunology | volume = 12 | issue = 1 | pages = 24–34 | date = December 2011 | pmid = 22158414 | pmc = 3947622 | doi = 10.1038/nri3128 }}</ref> Some memory B cells can be activated without T cell help, such as certain virus-specific memory B cells, but others need T cell help.<ref name=":12" /> Upon antigen binding, the memory B cell takes up the antigen through receptor-mediated endocytosis, degrades it, and presents it to T cells as peptide pieces in complex with MHC-II molecules on the cell membrane.<ref name=":13" /> Memory T helper (T<sub>H</sub>) cells, typically memory follicular T helper (T<sub>FH</sub>) cells, that were derived from T cells activated with the same antigen recognize and bind these MHC-II-peptide complexes through their TCR.<ref name=":13" /> Following TCR-MHC-II-peptide binding and the relay of other signals from the memory T<sub>FH</sub> cell, the memory B cell is activated and differentiates either into plasmablasts and plasma cells via an extrafollicular response or enter a germinal center reaction where they generate plasma cells and more memory B cells.<ref name=":13" /><ref name=":12" /> It is unclear whether the memory B cells undergo further affinity maturation within these secondary GCs.<ref name=":13" /> ''[[In vitro]]'' activation of memory B cells can be achieved through stimulation with various activators, such as pokeweed mitogen or anti-[[CD40 (protein)|CD40]] [[Monoclonal antibody|monoclonal antibodies]], however, a study found a combination of [[Resiquimod|R-848]] and [[Interleukin 2|recombinant human IL-2]] to be the most efficient activator.<ref>{{Cite journal |last1=Jahnmatz |first1=Maja |last2=Kesa |first2=Gun |last3=Netterlid |first3=Eva |last4=Buisman |first4=Anne-Marie |last5=Thorstensson |first5=Rigmor |last6=Ahlborg |first6=Niklas |date=2013-05-31 |title=Optimization of a human IgG B-cell ELISpot assay for the analysis of vaccine-induced B-cell responses |journal=Journal of Immunological Methods |language=en |volume=391 |issue=1 |pages=50–59 |doi=10.1016/j.jim.2013.02.009 |pmid=23454005 |issn=0022-1759|doi-access=free }}</ref>

== B cell types ==
[[File:Plasmablast, Wright stain.png|thumb|Plasmablast, [[Wright stain]].]]
; Plasmablast: A short-lived, proliferating antibody-secreting cell arising from B cell differentiation.<ref name=":0" /> Plasmablasts are generated early in an infection and their antibodies tend to have a weaker affinity towards their target antigen compared to plasma cell.<ref name=":8" /> Plasmablasts can result from T cell-independent activation of B cells or the extrafollicular response from T cell-dependent activation of B cells.<ref name=":0" />
; [[Plasma cell]]: A long-lived, non-proliferating antibody-secreting cell arising from B cell differentiation.<ref name=":0" /> There is evidence that B cells first differentiate into a plasmablast-like cell, then differentiate into a plasma cell.<ref name=":8" /> Plasma cells are generated later in an infection and, compared to plasmablasts, have antibodies with a higher affinity towards their target antigen due to affinity maturation in the germinal center (GC) and produce more antibodies.<ref name=":8" /> Plasma cells typically result from the germinal center reaction from T cell-dependent activation of B cells, though they can also result from T cell-independent activation of B cells.<ref name=":11" />
; Lymphoplasmacytoid cell: A cell with a mixture of B lymphocyte and plasma cell morphological features that is thought to be closely related to or a subtype of plasma cells. This cell type is found in pre-malignant and malignant [[plasma cell dyscrasia]]s that are associated with the secretion of [[IgM]] monoclonal proteins; these dyscrasias include [[Plasma cell dyscrasia#IgM MGUS|IgM monoclonal gammopathy of undetermined significance]] and [[Waldenström's macroglobulinemia]].<ref name="pmid25899140">{{cite journal | vauthors = Ribourtout B, Zandecki M | title = Plasma cell morphology in multiple myeloma and related disorders | journal = Morphologie | volume = 99 | issue = 325 | pages = 38–62 | date = June 2015 | pmid = 25899140 | doi = 10.1016/j.morpho.2015.02.001 | s2cid = 1508656 }}</ref>
; [[Memory B cell]]: Dormant B cell arising from B cell differentiation.<ref name=":0" /> Their function is to circulate through the body and initiate a stronger, more rapid antibody response (known as the anamnestic secondary antibody response) if they detect the antigen that had activated their parent B cell (memory B cells and their parent B cells share the same BCR, thus they detect the same antigen).<ref name=":12">{{cite journal | vauthors = Kurosaki T, Kometani K, Ise W | title = Memory B cells | journal = Nature Reviews. Immunology | volume = 15 | issue = 3 | pages = 149–159 | date = March 2015 | pmid = 25677494 | doi = 10.1038/nri3802 | s2cid = 20825732 }}</ref> Memory B cells can be generated from T cell-dependent activation through both the extrafollicular response and the germinal center reaction as well as from T cell-independent activation of B1 cells.<ref name=":12" />
; B-2 cell: FO B cells and MZ B cells.<ref name=":14" />
:; [[Follicular B cells|Follicular (FO) B cell]] (also known as a B-2 cell): Most common type of B cell and, when not circulating through the blood, is found mainly in the lymphoid follicles of secondary lymphoid organs (SLOs).<ref name=":8" /> They are responsible for generating the majority of high-affinity antibodies during an infection.<ref name=":0" />
:; [[Marginal-zone B cell|Marginal-zone (MZ) B cell]]: Found mainly in the marginal zone of the spleen and serves as a first line of defense against blood-borne pathogens, as the marginal zone receives large amounts of blood from the general circulation.<ref>{{cite journal | vauthors = Pillai S, Cariappa A, Moran ST | title = Marginal zone B cells | journal = Annual Review of Immunology | volume = 23 | issue = 1 | pages = 161–196 | date = 2005-01-01 | pmid = 15771569 | doi = 10.1146/annurev.immunol.23.021704.115728 }}</ref> They can undergo both T cell-independent and T cell-dependent activation, but preferentially undergo T cell-independent activation.<ref name=":8" />
; [[B-1 cell]]: Arises from a developmental pathway different from FO B cells and MZ B cells.<ref name=":14">{{cite journal | vauthors = Baumgarth N | title = The double life of a B-1 cell: self-reactivity selects for protective effector functions | journal = Nature Reviews. Immunology | volume = 11 | issue = 1 | pages = 34–46 | date = January 2011 | pmid = 21151033 | doi = 10.1038/nri2901 | s2cid = 23355423 }}</ref> In mice, they predominantly populate the [[peritoneal cavity]] and [[pleural cavity]], generate [[Antibody#Natural antibodies|natural antibodies]] (antibodies produced without infection), defend against mucosal pathogens, and primarily exhibit T cell-independent activation.<ref name=":14" /> A true homologue of mouse B-1 cells has not been discovered in humans, though various cell populations similar to B-1 cells have been described.<ref name=":14" />
; [[Regulatory B cells|Regulatory B (Breg) cell]]: An [[Immunosuppression|immunosuppressive]] B cell type that stops the expansion of pathogenic, pro-inflammatory lymphocytes through the secretion of IL-10, IL-35, and TGF-β.<ref name=":15">{{cite journal | vauthors = Rosser EC, Mauri C | title = Regulatory B cells: origin, phenotype, and function | journal = Immunity | volume = 42 | issue = 4 | pages = 607–612 | date = April 2015 | pmid = 25902480 | doi = 10.1016/j.immuni.2015.04.005 | doi-access = free }}</ref> Also, it promotes the generation of [[Regulatory T cell|regulatory T (Treg) cells]] by directly interacting with T cells to skew their differentiation towards Tregs.<ref name=":15" /> No common Breg cell identity has been described and many Breg cell subsets sharing regulatory functions have been found in both mice and humans.<ref name=":15" /> It is currently unknown if Breg cell subsets are developmentally linked and how exactly differentiation into a Breg cell occurs.<ref name=":15" /> There is evidence showing that nearly all B cell types can differentiate into a Breg cell through mechanisms involving inflammatory signals and BCR recognition.<ref name=":15" />

==B cell-related pathology==
Autoimmune disease can result from abnormal B cell recognition of self-antigens followed by the production of autoantibodies.<ref name=":16">{{cite journal | vauthors = Yanaba K, Bouaziz JD, Matsushita T, Magro CM, St Clair EW, Tedder TF | title = B-lymphocyte contributions to human autoimmune disease | journal = Immunological Reviews | volume = 223 | issue = 1 | pages = 284–299 | date = June 2008 | pmid = 18613843 | doi = 10.1111/j.1600-065X.2008.00646.x | s2cid = 11593298 }}</ref> Autoimmune diseases where disease activity is correlated with B cell activity include [[scleroderma]], [[multiple sclerosis]], [[systemic lupus erythematosus]], [[Diabetes mellitus type 1|type 1 diabetes]], [[Irritable bowel syndrome|post-infectious IBS]], and [[rheumatoid arthritis]].<ref name=":16" />

[[Malignant transformation]] of B cells and their precursors can cause a host of [[cancer]]s, including [[B-cell chronic lymphocytic leukemia|chronic lymphocytic leukemia (CLL)]], [[Acute lymphoblastic leukemia|acute lymphoblastic leukemia (ALL)]], [[hairy cell leukemia]], [[follicular lymphoma]], [[Non-Hodgkin lymphoma|non-Hodgkin's lymphoma]], [[Hodgkin's lymphoma]], and [[Plasma cell dyscrasia|plasma cell malignancies]] such  as [[multiple myeloma]], [[Waldenström's macroglobulinemia]], and certain forms of [[amyloidosis]].<ref>{{cite journal | vauthors = Shaffer AL, Young RM, Staudt LM | title = Pathogenesis of human B cell lymphomas | journal = Annual Review of Immunology | volume = 30 | issue = 1 | pages = 565–610 | date = 2012-01-01 | pmid = 22224767 | pmc = 7478144 | doi = 10.1146/annurev-immunol-020711-075027 }}</ref><ref name="pmid27866585">{{cite journal | vauthors = Castillo JJ | title = Plasma Cell Disorders | journal = Primary Care | volume = 43 | issue = 4 | pages = 677–691 | date = December 2016 | pmid = 27866585 | doi = 10.1016/j.pop.2016.07.002 }}</ref>

Abnormal B cells may be relatively large and some diseases include this in their names, such as [[diffuse large B-cell lymphoma]]s (DLBCLs) and [[intravascular large B-cell lymphoma]].

Patients with B cell alymphocytosis are predisposed to infections.<ref>Grammatikos Alexandros, Donati Matthew, Johnston Sarah L., Gompels Mark M. Peripheral B Cell Deficiency and Predisposition to Viral Infections: The Paradigm of Immune Deficiencies. Frontiers in Immunology (12)2021 https://www.frontiersin.org/articles/10.3389/fimmu.2021.731643 DOI=10.3389/fimmu.2021.731643</ref>

== Epigenetics ==
A study that investigated the [[methylome]] of B cells along their differentiation cycle, using [[Whole genome bisulfite sequencing|whole-genome bisulfite sequencing]] (WGBS), showed that there is a hypomethylation from the earliest stages to the most differentiated stages. The largest methylation difference is between the stages of germinal center B cells and memory B cells. Furthermore, this study showed that there is a similarity between B cell tumors and long-lived B cells in their [[DNA methylation]] signatures.<ref>{{cite journal | vauthors = Kulis M, Merkel A, Heath S, Queirós AC, Schuyler RP, Castellano G, Beekman R, Raineri E, Esteve A, Clot G, Verdaguer-Dot N, Duran-Ferrer M, Russiñol N, Vilarrasa-Blasi R, Ecker S, Pancaldi V, Rico D, Agueda L, Blanc J, Richardson D, Clarke L, Datta A, Pascual M, Agirre X, Prosper F, Alignani D, Paiva B, Caron G, Fest T, Muench MO, Fomin ME, Lee ST, Wiemels JL, Valencia A, Gut M, Flicek P, Stunnenberg HG, Siebert R, Küppers R, Gut IG, Campo E, Martín-Subero JI | display-authors = 6 | title = Whole-genome fingerprint of the DNA methylome during human B cell differentiation | journal = Nature Genetics | volume = 47 | issue = 7 | pages = 746–756 | date = July 2015 | pmid = 26053498 | pmc = 5444519 | doi = 10.1038/ng.3291 }}</ref>

== See also ==
* [[A20 cells]]
* [[List of distinct cell types in the adult human body]]

== References ==
{{Reflist|2}}

{{Lymphocytes}}
{{immune system}}
{{Authority control}}

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[[Category:B cells]]
[[Category:Lymphocytes]]
[[Category:Human cells]]
[[Category:Immunology]]
[[Category:Immune system]]