Signals 1, 2 and B cell fate or: Where, when and for how long?

• Published in: Immunological reviews 2020-07, Vol.296 (1), p.9-23
• Main Authors: Turner, Jackson S., Benet, Zachary L., Grigorova, Irina L.
• Format: Article
• Language: English
• Subjects: activation‐induced cell death; Anergy; Antibodies; Antigens; Autoantigens; Autoimmunity; B cell receptor signaling; Cell activation; Cell death; Cell fate; Cell proliferation; Cell survival; Humoral immunity; Immune response; Immune system; Immunological tolerance; Lymphocytes; Lymphocytes B; Lymphocytes T; Organs; T cell help; tolerance; T‐dependent B cell response; Vaccine development; Vaccines; Valency
• ISSN: 0105-2896; 1600-065X
• DOI: 10.1111/imr.12865

Diverse B cell responses are important for generating antibody‐mediated protection against highly variable pathogens. While some antigens can trigger T‐independent B cell proliferation and short‐term antibody production, development of long‐term humoral immunity requires T‐dependent B cell responses. The “two‐signal” model of B cell activation has long been invoked to explain alternate B cell recruitment into immune response to foreign antigens vs. induction of tolerance to self‐antigens. However, a number of other factors appear to influence the fate of mature B cells responding to antigen in vivo. In this review, we will discuss how various spatiotemporal scenarios of antigen access into secondary lymphoid organs, antigen valency and cellular environment of antigen acquisition by B cells, duration of B cell access to antigen and the timing of T cell help may affect follicular B cell fate, including death, survival, anergy, and recruitment into T‐dependent responses. We will also highlight unresolved questions related to B cell activation and tolerance in vivo that may have important implications for vaccine development and autoimmunity.