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.

B cells rapidly target antigen and surface-derived MHCII into peripheral degradative compartments

“…1A). MVBs are typically considered to represent late endosomes, and for MIICs, MVB-like structures have been characterized after 1h of activation in the perinuclear region (Adler et al, 2017; Lankar et al, 2002; Unanue et al, 2016; Vascotto et al, 2007b). While multivesicular morphology has been linked to MHCII loading (Roche and Furuta, 2015; Lith et al, 2001; Xiu et al, 2011), the localization of antigen into multivesicular structures raised the question whether already at 15 min after activation, in the cell periphery, antigen could be in MIIC.…”

“…The MHCII peptide-loading compartment (MIIC), where antigen is processed into peptides for loading onto MHCII molecules, is characterized by its main hallmarks, antigen and MHCII. In addition, MIIC contains the key peptide loading chaperone H2-M and the proteolytic enzyme Cathepsin-S (Adler et al, 2017). MIIC has been well characterized by various biochemical fractionation techniques.…”

Immune responses induced by recombinant Lactobacillus plantarum expressing the spike protein derived from transmissible gastroenteritis virus in piglets

“…In previous reports, this vaccine strategy offered a variety of benefits in that the constructed L. plantarum expression of protein-fused DCpep could activate mucosal DCs, B cells, and T cells to induce the immunological response and could regulate inflammatory responses that took place in a mucosal microenvironment (Steinman and Idoyaga 2010). Our laboratory has previously studied Yang et al 2016) the effects of recombinant lactic acid bacteria expressing target antigens and DCpep on MHC-II + CD80 + DCs; however, the impact of recombinant lactic acid bacteria cells has not been studied in MHC-II + CD80 + B (such cells not only can secrete SIgA involved in mucosal immunity but also can act as antigen-presenting cells) (Adler et al 2017;Mizoguchi and Bhan 2017). Therefore, in this study, we mainly researched the effects of recombinant lactic acid bacteria NC8-pSIP409-pgsA-S-DCpep expressing DCpep and target antigen S protein on MHC-II + CD80 + B cells, CD3 + CD4 + cells related to mucosal immune responses, and anti-TGEVspecific antibodies.…”

CD4 T cells in protection from influenza virus: Viral antigen specificity and functional potential

“…Not only does antigen engagement through the Ig receptor promote a profoundly increased efficiency of the capture of limiting amounts of antigen (estimated by an early study to be in the range of 1000 to 10,000 fold (120)), but this binding event also signals the B cells. Ig-mediated internalization and signaling leads to many intracellular alterations that are important for antigen processing and presentation of peptide:MHC class II proteins (reviewed in (121, 122)). Engagement of the B cell receptor with antigen-bearing cells such as follicular dendritic cells, DCs (123) and macrophages at the follicle-SCS boundary (124) allows multivalent interactions and sustained B cell receptor-mediated signaling and later B cell differentiation (reviewed in (125–127)).…”

“…Not only does antigen engagement through the Ig receptor promote a profoundly increased efficiency of the capture of limiting amounts of antigen (estimated by an early study to be in the range of 1000-10 000 fold 120 ), but this binding event also signals the B cells. Ig-mediated internalization and signaling leads to many intracellular alterations that are important for antigen processing and presentation of peptide:MHC class II proteins (reviewed in 121,122 ).…”