CD40 signaling activates CD11a/CD18 (LFA-1)-mediated adhesion in B cells.
Cell-cell adhesion events play critical roles in the sequential migrations and multiple specific cell-cell interactions which B cells undergo during normal development and function. We have observed that mAb to several B cell-associated molecules, including mAb to CD19, CD37, and CD40, induce homotypic aggregation of freshly isolated human B cells. The aggregation of B cells induced by CD40 mAb was due to activation of a cell-cell adhesion system, and not due to agglutination by mAb, because 1) in addition to being energy dependent and cation dependent, the aggregation was blocked by inhibitors of messenger RNA and protein synthesis; and 2) a mouse B cell line transformed with intact human CD40 aggregated in response to CD40 mAb, whereas a line expressing surface CD40, but lacking the cytoplasmic tail and previously shown incapable of transmitting a signal from the cell surface, did not aggregate. The aggregation, although of slow onset, was persistent and of high avidity. In addition, CD40 mAb induced increased surface expression of intercellular adhesion molecule-1 (CD54), a ligand for CD11a/CD18 (LFA-1), and CD18 mAb blocked aggregation. CD40 mAb also augmented the ability of dense B cells to stimulate the proliferation of allogeneic T cells via a CD18-dependent process. We conclude that signaling through CD40, elicited by cross-linking the CD40 protein on the cell surface, activates the CD18/intercellular adhesion molecule adhesion system; in addition, CD40 cross-linking may activate a second adhesion system since CD40 mAb induced aggregation of the B cell line Ramos, which does not express surface CD18. B cell adhesion may be triggered by signaling through multiple surface proteins, thereby lending specificity of activation to adhesion systems which are broadly expressed.
Barrett
T B
TB
Department of Microbiology, University of Washington, Seattle 98195.
Shu
G
G
Clark
E A
EA
D000818:Animals; D000911:Antibodies, Monoclonal; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology*; D018821:CD18 Antigens; D019013:CD40 Antigens; D002412:Cations; D002448:Cell Adhesion / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002449:Cell Aggregation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D007141:Immunoglobulin Fc Fragments / Q000502:physiology; D018799:Intercellular Adhesion Molecule-1; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D051379:Mice; D016028:Receptors, Leukocyte-Adhesion / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection
D000911:Antibodies, Monoclonal; D000944:Antigens, Differentiation, B-Lymphocyte; D018821:CD18 Antigens; D019013:CD40 Antigens; D002412:Cations; D015815:Cell Adhesion Molecules; D007141:Immunoglobulin Fc Fragments; D016169:Lymphocyte Function-Associated Antigen-1; D016028:Receptors, Leukocyte-Adhesion; D018799:Intercellular Adhesion Molecule-1