Editing B cell (section)

===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" />