CD48 delivers an accessory signal for CD40-mediated activation of human B cells.
CD48, a glycosyl phosphatidylinositol anchored molecule has recently been shown to be a ligand for the T cell surface protein CD2 in mouse, human, and rat. It is expressed on practically all human T and B cells; however, its function remains unknown. We examined whether CD48 may be involved in the delivery of activating signals to human B cells. Costimulation with anti-CD48 J4-57 significantly increased CD40-mediated activation of tonsillar B cells. Costimulatory effect of anti-CD48 was observed on B cell aggregation, proliferation, and IgG secretion. Anti-CD48 alone did not stimulate resting B cells. Accessory signal provided through CD48 required the presence of IL-4 and/or IL-10, whereas responses of B cells to IL-2 was not affected. Ligation of CD48 by specific antibody induced CD23 expression on IL-4-stimulated Ramos B cell line but did not affect expression of CD25. We also examined the biochemical nature of the costimulatory effect of anti-CD40 and CD48. Ligation of CD40 or CD48 on the B cells induced tyrosine phosphorylation of proteins. CD40 induced earlier changes in the protein phosphorylation than CD48 did. Taken together, our data suggest that the stimulation via CD40 provides initial signals to activate B cells and CD48 may be involved in enhancing the activating signal to B cells, resulting in increased responsiveness of B cells to IL-4 and IL-10.
Klyushnenkova
E N
EN
Laboratory of Cellular Immunology, Alton Ochsner Medical Foundation, New Orleans, Louisiana 70121, USA.
Li
L
L
Armitage
R J
RJ
Choi
Y S
YS
D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology*; D023201:CD40 Ligand; D000071178:CD48 Antigen; D002449:Cell Aggregation; D002478:Cells, Cultured; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D016753:Interleukin-10 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000276:immunology; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D017455:Receptors, IgE / Q000096:biosynthesis; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D019013:CD40 Antigens; D000071178:CD48 Antigen; C000604065:CD48 protein, human; C000604066:Cd48 protein, mouse; C000604067:Cd48 protein, rat; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D011506:Proteins; D017455:Receptors, IgE; D015375:Receptors, Interleukin-2; D016753:Interleukin-10; D023201:CD40 Ligand; D015847:Interleukin-4; D019000:Phosphotyrosine