title: The Other Function: Class II-Restricted Antigen Presentation by B Cells.
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.
authors.affiliation: Department of Pediatrics, Stanford University, Stanford, CA, USA; Program in Immunology, Stanford University, Stanford, CA, USA.
authors.forename: Lital N
authors.initials: LN
authors.lastname: Adler
authors.affiliation: Department of Pediatrics, Stanford University, Stanford, CA, USA; Program in Immunology, Stanford University, Stanford, CA, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Program in Immunology, Stanford University , Stanford, CA , USA.
authors.forename: Kartik
authors.initials: K
authors.lastname: Bhamidipati
authors.affiliation: Stanford University , Stanford, CA , USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Millican
authors.affiliation: Department of Pediatrics, Stanford University, Stanford, CA, USA; Program in Immunology, Stanford University, Stanford, CA, USA.
authors.forename: Claudia
authors.initials: C
authors.lastname: Macaubas
authors.affiliation: Department of Pediatrics, Stanford University, Stanford, CA, USA; Program in Immunology, Stanford University, Stanford, CA, USA.
authors.forename: Shu-Chen
authors.initials: SC
authors.lastname: Hung
authors.affiliation: Department of Pediatrics, Stanford University, Stanford, CA, USA; Program in Immunology, Stanford University, Stanford, CA, USA.
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Mellins
keywords: B cell; HLA-DM; HLA-DO; MHC class II; antigen presentation; antigen processing; germinal center; invariant chain