Minding the gap: The impact of B‐cell tolerance on the microbial antibody repertoire
Year: 2019
Type: review
Abstract: B lymphocytes must respond to vast numbers of foreign antigens, including those of microbial pathogens. To do so, developing B cells use combinatorial joining of V-, D-, and J-gene segments to generate an extraordinarily diverse repertoire of B-cell antigen receptors (BCRs). Unsurprisingly, a large fraction of this initial BCR repertoire reacts to self-antigens, and these "forbidden" B cells are culled by immunological tolerance from mature B-cell populations. While culling of autoreactive BCRs mitigates the risk of autoimmunity, it also opens gaps in the BCR repertoire, which are exploited by pathogens that mimic the forbidden self-epitopes. Consequently, immunological tolerance, necessary for averting autoimmune disease, also acts to limit effective microbial immunity. In this brief review, we recount the evidence for the linkage of tolerance and impaired microbial immunity, consider the implications of this linkage for vaccine development, and discuss modulating tolerance as a potential strategy for strengthening humoral immune responses.
Source: Immunological Reviews
DOI: 10.1111/imr.12805
Institution: Duke University
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Awards: Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, Modeling affinity maturation at molecular resolution, Basic Immunology Training Program, G9000028040, G9000129325, G9000337902, Structure-function analysis of infection- and vaccine-induced B-cell repertoires, Cancer Center Support Grant (CCSG)
OpenAlex ID: W2975002111