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The term [[humoral immunity]] is often treated as synonymous with the antibody response, describing the function of the immune system that exists in the body's humors (fluids) in the form of soluble proteins, as distinct from [[cell-mediated immunity]], which generally describes the responses of [[T cell]]s (especially cytotoxic T cells). In general, antibodies are considered part of the [[adaptive immune system]], though this classification can become complicated. For example, natural IgM,<ref>{{Cite journal |last1=Ehrenstein |first1=Michael R. |last2=Notley |first2=Clare A. |date=2010-10-15 |title=The importance of natural IgM: scavenger, protector and regulator |url=http://dx.doi.org/10.1038/nri2849 |journal=Nature Reviews Immunology |volume=10 |issue=11 |pages=778–786 |doi=10.1038/nri2849 |pmid=20948548 |s2cid=35784099 |issn=1474-1733}}</ref> which are made by B-1 lineage cells that have properties more similar to innate immune cells than adaptive, refers to IgM antibodies made independently of an immune response that demonstrate polyreactivity- they recognize multiple distinct (unrelated) antigens. These can work with the [[complement system]] in the earliest phases of an immune response to help facilitate clearance of the offending antigen and delivery of the resulting [[Immune complex|immune complexes]] to the [[Lymph node|lymph nodes]] or [[spleen]] for initiation of an immune response. Hence in this capacity, the function of antibodies is more akin to that of innate immunity than adaptive. Nonetheless, in general antibodies are regarded as part of the adaptive immune system because they demonstrate exceptional specificity (with some exception), are produced through genetic rearrangements (rather than being encoded directly in [[germline]]), and are a manifestation of immunological memory.
In the course of an immune response, B cells can progressively [[Cellular differentiation|differentiate]] into antibody-secreting cells (B cells themselves do not secrete antibody; B cells do, however, express B cell receptors, the membrane-bound form of the antibody, on their surface) or memory B cells.<ref>{{Cite journal |last1=Akkaya |first1=Munir |last2=Kwak |first2=Kihyuck |last3=Pierce |first3=Susan K. |date=April 2020 |title=B cell memory: building two walls of protection against pathogens |journal=Nature Reviews Immunology |language=en |volume=20 |issue=4 |pages=229–238 |doi=10.1038/s41577-019-0244-2 |pmid=31836872 |pmc=7223087 |issn=1474-1741}}</ref> Antibody-secreting cells comprise plasmablasts and [[Plasma cell|plasma cells]], which differ mainly in the degree to which they secrete antibody, their lifespan, metabolic adaptations, and surface markers.<ref>{{Cite journal |last1=Tellier |first1=Julie |last2=Nutt |first2=Stephen L |date=2018-10-15 |title=Plasma cells: The programming of an antibody-secreting machine |url=http://dx.doi.org/10.1002/eji.201847517 |journal=European Journal of Immunology |volume=49 |issue=1 |pages=30–37 |doi=10.1002/eji.201847517 |pmid=30273443 |issn=0014-2980|hdl=11343/284565 |hdl-access=free }}</ref> Plasmablasts are rapidly proliferating, short-lived cells produced in the early phases of the immune response (classically described as arising extrafollicularly rather than from the [[germinal center]]) which have the potential to differentiate further into plasma cells.<ref>{{Citation |title=B Cell Memory and Plasma Cell Development |date=2015 |work=Molecular Biology of B Cells |pages=227–249 |url=https://linkinghub.elsevier.com/retrieve/pii/B978012397933900014X |access-date=2024-01-24 |publisher=Elsevier |language=en |doi=10.1016/b978-0-12-397933-9.00014-x |isbn=978-0-12-397933-9}}</ref> The literature is sloppy at times and often describes plasmablasts as just short-lived plasma cells- formally this is incorrect. Plasma cells, in contrast, do not divide (they are [[terminally differentiated]]), and rely on survival niches comprising specific cell types and cytokines to persist.<ref>{{Cite journal |last1=Chu |first1=Van T. |last2=Berek |first2=Claudia |date=2012-12-19 |title=The establishment of the plasma cell survival niche in the bone marrow |url=http://dx.doi.org/10.1111/imr.12011 |journal=Immunological Reviews |volume=251 |issue=1 |pages=177–188 |doi=10.1111/imr.12011 |pmid=23278749 |s2cid=205212187 |issn=0105-2896}}</ref> Plasma cells will secrete huge quantities of antibody regardless of whether or not their cognate antigen is present, ensuring that antibody levels to the antigen in question do not fall to 0, provided the plasma cell stays alive. The rate of antibody secretion, however, can be regulated, for example, by the presence of adjuvant molecules that stimulate the immune response such as [[Toll-like receptor|TLR]] ligands.<ref>{{Cite journal |last1=Dorner |first1=Marcus |last2=Brandt |first2=Simone |last3=Tinguely |first3=Marianne |last4=Zucol |first4=Franziska |last5=Bourquin |first5=Jean-Pierre |last6=Zauner |first6=Ludwig |last7=Berger |first7=Christoph |last8=Bernasconi |first8=Michele |last9=Speck |first9=Roberto F. |last10=Nadal |first10=David |date=2009-11-06 |title=Plasma cell toll-like receptor (TLR) expression differs from that of B cells, and plasma cell TLR triggering enhances immunoglobulin( MAGED ) production |url=http://dx.doi.org/10.1111/j.1365-2567.2009.03143.x |journal=Immunology |volume=128 |issue=4 |pages=573–579 |doi=10.1111/j.1365-2567.2009.03143.x |pmid=19950420 |pmc=2792141 |issn=0019-2805}}</ref> Long-lived plasma cells can live for potentially the entire lifetime of the organism.<ref>{{Cite journal |last1=Joyner |first1=Chester J. |last2=Ley |first2=Ariel M. |last3=Nguyen |first3=Doan C. |last4=Ali |first4=Mohammad |last5=Corrado |first5=Alessia |last6=Tipton |first6=Christopher |last7=Scharer |first7=Christopher D. |last8=Mi |first8=Tian |last9=Woodruff |first9=Matthew C. |last10=Hom |first10=Jennifer |last11=Boss |first11=Jeremy M. |last12=Duan |first12=Meixue |last13=Gibson |first13=Greg |last14=Roberts |first14=Danielle |last15=Andrews |first15=Joel |date=March 2022 |title=Generation of human long-lived plasma cells by developmentally regulated epigenetic imprinting |journal=Life Science Alliance |volume=5 |issue=3 |pages=e202101285 |doi=10.26508/lsa.202101285 |issn=2575-1077 |pmc=8739272 |pmid=34952892}}</ref> Classically, the survival niches that house long-lived plasma cells reside in the bone marrow,<ref>{{Cite journal |last1=Halliley |first1=Jessica L. |last2=Tipton |first2=Christopher M. |last3=Liesveld |first3=Jane |last4=Rosenberg |first4=Alexander F. |last5=Darce |first5=Jaime |last6=Gregoretti |first6=Ivan V. |last7=Popova |first7=Lana |last8=Kaminiski |first8=Denise |last9=Fucile |first9=Christopher F. |last10=Albizua |first10=Igor |last11=Kyu |first11=Shuya |last12=Chiang |first12=Kuang-Yueh |last13=Bradley |first13=Kyle T. |last14=Burack |first14=Richard |last15=Slifka |first15=Mark |date=July 2015 |title=Long-Lived Plasma Cells Are Contained within the CD19−CD38hiCD138+ Subset in Human Bone Marrow |journal=Immunity |language=en |volume=43 |issue=1 |pages=132–145 |doi=10.1016/j.immuni.2015.06.016 |pmc=4680845 |pmid=26187412}}</ref> though it cannot be assumed that any given plasma cell in the bone marrow will be long-lived. However, other work indicates that survival niches can readily be established within the mucosal tissues- though the classes of antibodies involved show a different hierarchy from those in the bone marrow.<ref>{{Cite journal |last1=Tellier |first1=Julie |last2=Tarasova |first2=Ilariya |last3=Nie |first3=Junli |last4=Smillie |first4=Christopher S. |last5=Fedele |first5=Pasquale L. |last6=Cao |first6=Wang H. J. |last7=Groom |first7=Joanna R. |last8=Belz |first8=Gabrielle T. |last9=Bhattacharya |first9=Deepta |last10=Smyth |first10=Gordon K. |last11=Nutt |first11=Stephen L. |date=2024-01-03 |title=Unraveling the diversity and functions of tissue-resident plasma cells |url=http://dx.doi.org/10.1038/s41590-023-01712-w |journal=Nature Immunology |volume=25 |issue=2 |pages=330–342 |doi=10.1038/s41590-023-01712-w |pmid=38172260 |s2cid=266752931 |issn=1529-2908}}</ref><ref>{{Cite journal |last1=Landsverk |first1=Ole J. B. |last2=Snir |first2=Omri |last3=Casado |first3=Raquel Bartolomé |last4=Richter |first4=Lisa |last5=Mold |first5=Jeff E. |last6=Réu |first6=Pedro |last7=Horneland |first7=Rune |last8=Paulsen |first8=Vemund |last9=Yaqub |first9=Sheraz |last10=Aandahl |first10=Einar Martin |last11=Øyen |first11=Ole M. |last12=Thorarensen |first12=Hildur Sif |last13=Salehpour |first13=Mehran |last14=Possnert |first14=Göran |last15=Frisén |first15=Jonas |date=February 2017 |title=Antibody-secreting plasma cells persist for decades in human intestine |journal=The Journal of Experimental Medicine |volume=214 |issue=2 |pages=309–317 |doi=10.1084/jem.20161590 |issn=1540-9538 |pmc=5294861 |pmid=28104812}}</ref> B cells can also differentiate into memory B cells which can persist for decades similarly to long-lived plasma cells. These cells can be rapidly recalled in a secondary immune response, undergoing class switching, affinity maturation, and differentiating into antibody-secreting cells.
Antibodies are central to the immune protection elicited by most vaccines and infections (although other components of the immune system certainly participate and for some diseases are considerably more important than antibodies in generating an immune response, e.g. [[Shingles|herpes zoster]]).<ref>{{Cite journal |last=Plotkin |first=Stanley A. |date=2022 |title=Recent updates on correlates of vaccine-induced protection |journal=Frontiers in Immunology |volume=13 |pages=1081107 |doi=10.3389/fimmu.2022.1081107 |doi-access=free |issn=1664-3224 |pmc=9912984 |pmid=36776392}}</ref> Durable protection from infections caused by a given microbe – that is, the ability of the microbe to enter the body and begin to replicate (not necessarily to cause disease) – depends on sustained production of large quantities of antibodies, meaning that effective vaccines ideally elicit persistent high levels of antibody, which relies on long-lived plasma cells. At the same time, many microbes of medical importance have the ability to mutate to escape antibodies elicited by prior infections, and long-lived plasma cells cannot undergo affinity maturation or class switching. This is compensated for through memory B cells: novel variants of a microbe that still retain structural features of previously encountered antigens can elicit memory B cell responses that adapt to those changes. It has been suggested that long-lived plasma cells secrete B cell receptors with higher affinity than those on the surfaces of memory B cells, but findings are not entirely consistent on this point.<ref>{{Cite journal |last1=Sutton |first1=Henry J. |last2=Gao |first2=Xin |last3=Kelly |first3=Hannah G. |last4=Parker |first4=Brian J. |last5=Lofgren |first5=Mariah |last6=Dacon |first6=Cherrelle |last7=Chatterjee |first7=Deepyan |last8=Seder |first8=Robert A. |last9=Tan |first9=Joshua |last10=Idris |first10=Azza H. |last11=Neeman |first11=Teresa |last12=Cockburn |first12=Ian A. |date=2024-01-12 |title=Lack of affinity signature for germinal center cells that have initiated plasma cell differentiation |url=https://pubmed.ncbi.nlm.nih.gov/38228150 |journal=Immunity |volume=57 |issue=2 |pages=S1074–7613(23)00541–1 |doi=10.1016/j.immuni.2023.12.010 |issn=1097-4180 |pmid=38228150|pmc=10922795 |pmc-embargo-date=February 13, 2025 }}</ref>
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