BCR Affinity Influences T-B Interactions and B Cell Development in Secondary Lymphoid Organs.

Alec J Wishnie,Tzippora Chwat-Edelstein,Mary Attaway,Bao Q Vuong

doi:10.3389/fimmu.2021.703918

Abstract

B cells produce high-affinity immunoglobulins (Igs), or antibodies, to eliminate foreign pathogens. Mature, naïve B cells expressing an antigen-specific cell surface Ig, or B cell receptor (BCR), are directed toward either an extrafollicular (EF) or germinal center (GC) response upon antigen binding. B cell interactions with CD4+ pre-T follicular helper (pre-Tfh) cells at the T-B border and effector Tfh cells in the B cell follicle and GC control B cell development in response to antigen. Here, we review recent studies demonstrating the role of B cell receptor (BCR) affinity in modulating T-B interactions and the subsequent differentiation of B cells in the EF and GC response. Overall, these studies demonstrate that B cells expressing high affinity BCRs preferentially differentiate into antibody secreting cells (ASCs) while those expressing low affinity BCRs undergo further affinity maturation or differentiate into memory B cells (MBCs).

Highlights

B cells mediate the humoral immune response through the production of antigen-specific immunoglobulins (Igs) that neutralize foreign pathogens [1]
Through increased inducible T cell costimulator ligand (ICOSL) expression and antigen presentation on MHCII, B cells with high affinity B cell receptor (BCR) induce increased Ca2+ signaling in T follicular helper (Tfh) cells, which will in turn secrete higher levels of IL-21 or IL-4 (Figures 2, 3) [13].This suggests that these cytokines act as B cell extrinsic signals that direct B cell development based on BCR affinity, a B cell intrinsic characteristic [13]
Even though B cell development has been extensively studied, the regulatory mechanisms that control this process are still being explored with new models and genetic engineering tools such as CRISPR

Summary

Introduction

B cells mediate the humoral immune response through the production of antigen-specific immunoglobulins (Igs) that neutralize foreign pathogens [1]. Inhibiting ICOS-ICOSL interactions with a a-ICOSL antibody in MD4 mice immunized with DEL, but not HEL, prevents Tfh differentiation in vivo, suggesting that naïve B cells expressing low affinity BCRs promote Tfh differentiation in vivo through ICOSL [20].

Results

Conclusion