A role for the VLA-4 integrin in the activation of human memory B cells.
It is generally recognized that activation through membrane effector molecules such as CD40 or the B cell receptor (BCR) is mandatory to allow B cells to proliferate and differentiate into antibody (Ab)-secreting cells in response to cytokines. We show here that purified tonsillar B cells can be stimulated directly by a cytokine combination to proliferate and secrete immunoglobulins when cultures are performed at high cell density. The contact-mediated activation of B cells in this experimental system is strongly inhibited both by anti-very late antigen (VLA)-4 monoclonal Ab and by a peptide containing the LDV sequence specifically recognized by the alpha 4 integrin binding site. These reagents also significantly suppressed the B cell responses elicited by engagement of the BCR or CD40. Our data reveal that memory B cells but not virgin or germinal center B cells are sensitive to the direct stimulatory effect of cytokines in high-density cultures. Finally, we found that the dual expression of the alpha and beta chains of VLA-4 is a distinctive feature of the memory B cell population. Collectively, our findings support the notion that VLA-4-dependent homotypic B cell interactions can mediate a co-stimulatory signal to human memory B cells and might participate in the B cell activation triggered through the BCR and CD40.
Silvy
A
A
INSERM U 404, Immunité et Vaccination, Lyon, France.
Altevogt
P
P
Mondière
P
P
Bella
C
C
Defrance
T
T
D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D019013:CD40 Antigens / Q000502:physiology; D002450:Cell Communication / Q000187:drug effects; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D007156:Immunologic Memory / Q000187:drug effects; D039041:Integrin alpha4beta1; D039641:Integrin beta Chains; D016023:Integrins / Q000096:biosynthesis / Q000502:physiology*; D016753:Interleukin-10 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D016201:Receptors, Lymphocyte Homing / Q000096:biosynthesis / Q000502:physiology*; D016029:Receptors, Very Late Antigen / Q000096:biosynthesis / Q000502:physiology*
D019013:CD40 Antigens; D007136:Immunoglobulins; D039041:Integrin alpha4beta1; D039641:Integrin beta Chains; D016023:Integrins; D007376:Interleukin-2; D016201:Receptors, Lymphocyte Homing; D016029:Receptors, Very Late Antigen; C091368:integrin beta7; D016753:Interleukin-10