Abstract
Mature B lymphocytes (B cells) recognize antigens using their B cell receptor (BCR) and are activated to become antibody-producing cells. In addition, and integral to the development of a high-affinity antibodies, B cells utilize the specialized major histocompatibility complex class II (MHCII) antigen presentation pathway to process BCR-bound and internalized protein antigens and present selected peptides in complex with MHCII to CD4+ T cells. This interaction influences the fate of both types of lymphocytes and shapes immune outcomes. Specific, effective, and optimally timed antigen presentation by B cells requires well-controlled intracellular machinery, often regulated by the combined effects of several molecular events. Here, we delineate and summarize these events in four steps along the antigen presentation pathway: (1) antigen capture and uptake by B cells; (2) intersection of internalized antigen/BCRs complexes with MHCII in peptide-loading compartments; (3) generation and regulation of MHCII/peptide complexes; and (4) exocytic transport for presentation of MHCII/peptide complexes at the surface of B cells. Finally, we discuss modulation of the MHCII presentation pathway across B cell development and maturation to effector cells, with an emphasis on the shaping of the MHCII/peptide repertoire by two key antigen presentation regulators in B cells: HLA-DM and HLA-DO.
Highlights
In addition to their role as secretors of antibodies, B cells function as professional antigen-presenting cells (APCs) for CD4+ T cells by expressing cell-surface major histocompatibility complex class II (MHCII) molecules with bound peptide, the ligand of the α/β T cell receptor
We review the shaping of the MHCII/peptide repertoire by HLA-DM and HLA-DO and the MHCII/peptide complex transport to the surface of B cells
This review focuses on the class II antigen presentation pathway in B-2 cells
Summary
In addition to their role as secretors of antibodies, B cells function as professional antigen-presenting cells (APCs) for CD4+ T cells by expressing cell-surface major histocompatibility complex class II (MHCII) molecules with bound peptide, the ligand of the α/β T cell receptor. Recent evidence supports a model of sequential class II-restricted antigen presentation by thymic B cells to CD4+ thymocytes [1]. In this scenario, resting IgD+/IgM+ B cells enter the thymus and undergo cognate interactions with CD4+ thymocytes and CD40-mediated B cell activation. This increases MHCII, CD80, and Aire expression, allowing B cell presentation of Aire-dependent antigens and negative selection of self-antigen reactive thymocytes. This review focuses on the class II antigen presentation pathway in B-2 cells (referred to as B cells in what follows)
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