The Other Function: Class II-Restricted Antigen Presentation by B Cells

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 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/B cell receptors complexes with MHCII in peptide loading compartments; 3) generation and regulation of MHCII/peptide complexes; 4) exocytic transport for presentation of MHCII/peptide complexes at the surface of B cells. Last, we discuss modulation of the MHCII presentation pathway across B 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.