A ROLE FOR THE VLA-4 INTEGRIN IN THE ACTIVATION OF HUMAN-MEMORY B-CELLS

It is generally recognized that activation through membrane effector m olecules such as CD40 or the B cell receptor (BCR) is mandatory to all ow B cells to proliferate and differentiate into antibody (Ab)-secreti ng cells in response to cytokines. We show here that purified tonsilla r B cells can be stimulated directly by a cytokine combination to prol iferate and secrete immunoglobulins when cultures are performed at hig h cell density. The contact-mediated activation of B cells in this exp erimental system is strongly inhibited both by anti-very late antigen (VLA)-4 monoclonal Ab and by a peptide containing the LDV sequence spe cifically recognized by the alpha 4 integrin binding site. These reage nts also significantly suppressed the B cell responses elicited by eng agement of the BCR or CD40. Our data reveal that memory B cells but no t virgin or germinal center B cells are sensitive to the direct stimul atory 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 di stinctive feature of the memory B cell population. Collectively, our f indings support the notion that VLA-4-dependent homotypic B cell inter actions can mediate a co-stimulatory signal to human memory B cells an d might participate in the B cell activation triggered through the BCR and CD40.