Differential abilities of human peripheral blood monocytes quantitatively or qualitatively differing in HLA-DR and HLA-DS expression to support B cell activation in liquid and semisolid cultures.
The present investigation was performed to determine whether the activation of human B cells by Staphylococcal protein A (SpA) in liquid and semi-solid cultures might be dependent on distinct subsets of peripheral blood mononuclear-phagocytes (M phi) defined by the expression of HLA-DR and HLA-DS determinants. Highly pure HLA-DR- M phi functioned as effectively as HLA-DR+ MO in supporting B cell liquid proliferative responses when SpA was continuously present in cultures. However, HLA-DR+ M phi were two to three times more effective than HLA-DR- M phi in promoting B cell proliferative responses when either M phi or B cells were pulsed with SpA and were then cultured without supplemental SpA. Similarly, B cell activation in semisolid cultures was crucially dependent on HLA-DR+ M phi because colony responses were reduced fivefold in the presence of M phi expressing low/intermediate HLA-DR levels compared to M phi-containing cells with high HLA-DR levels. HLA-DS- M phi isolated by two different techniques were more effective than HLA-DS+ M phi in supporting both liquid proliferative and colony responses of B cells. Flow microcytofluorometry analysis of the dual expression of HLA-DR and HLA-DS on highly pure HLA-DR- M phi and HLA-DR+ M phi revealed that both HLA-DR- and HLA-DR+ M phi expressed low levels of HLA-DS. Importantly, the expression of HLA-DS on HLA-DR- M phi was bimodal, with an HLA-DR-, DS+ subset and an HLA-DR-, DS-subset being present. Other experiments supported the conclusions that the differential abilities of the HLA-DR-, -DS-defined subsets of M phi to support B cell activation did not represent M phi suppressive effects or differences in IL 1 production. Collectively, these results indicate that B cell activation can be directly supported by M phi whose predominant phenotype is HLA-DR+, -DS-. Thus, the accessory cell pathway of B cell activation described here is distinct from the pathway known to be required for T cell responsiveness, and could serve to provide early alternative or ancillary signals for triggering B cells.
D000328:Adult; D000938:Antigen-Presenting Cells / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D009000:Monocytes / Q000145:classification* / Q000276:immunology; D010641:Phenotype; D013205:Staphylococcal Protein A / Q000494:pharmacology
D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D013205:Staphylococcal Protein A