Editing B cell (section)

==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 | pages = 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 | 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" />