CD38 cross-linking enhances TLR-induced B cell proliferation but decreases IgM plasma cell differentiation.
It is becoming increasingly clear that the regulation of proliferation and differentiation of B cells to plasma cells involves the integration of a variety of intracellular signals provided by receptors of both the adaptive and innate immune system. The cross-linking of the surface molecule CD38 induces calcium mobilization, protein phosphorylation and NF-kappaB translocation into the nucleus, ultimately leading to proliferation and isotype switching toward IgG1. Here we describe (a) the effect on B cell activation of stimulating through both CD38 and Toll-like receptors 4, 7 and 9; and (b) that CD38 cross-linking increases the number of proliferating cells and the rate of proliferation in LPS-stimulated B cells by a Bruton's tyrosine kinase- and protein kinase C-dependent mechanism. In contrast, CD38 cross-linking reduces the number of cells committed to IgM plasma cell differentiation as measured by the number of CD138+ cells, antibody secretion, and the expression of PAX5, Bcl6 and Blimp-1. Since a putative ligand for CD38 is expressed by germinal center follicular dendritic cells, and CD38 expression is down-regulated in germinal center B cells, we speculate that CD38 might participate in the outcome of post-germinal center antibody responses.
Manjarrez-Orduño
Nataly
N
Molecular Biomedicine Department, Centro de Investigación y de Estudios Avanzados del IPN, Mexico City, México.
Moreno-García
Miguel E
ME
Fink
Katja
K
Santos-Argumedo
Leopoldo
L
D051997:ADP-ribosyl Cyclase 1 / Q000276:immunology*; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D015153:Blotting, Western; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D056742:Cyclin D2; D016213:Cyclins / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology*
C486196:Ccnd2 protein, mouse; D056742:Cyclin D2; D016213:Cyclins; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; D051193:Toll-Like Receptors; D051997:ADP-ribosyl Cyclase 1