Activation-dependent modulation of B lymphocyte migration to chemokines

Abstract

In this study we have examined the migration responses of human peripheral blood or tonsillar B lymphocytes to a selection of 27 chemokines. Freshly isolated (CD19+) B lymphocytes show greatly impaired in vitro chemotaxis which is overcome by overnight culture. The best responses of cultured B lymphocytes were observed with BCA-1, SLC, ELC and SDF-1, reaching 19-26% of total input cells that have migrated, followed by LARC and TECK with 5-10% of migrated cells, whereas no other chemokine was found to be active. Stimulation of B lymphocytes with lipopolysaccharide or anti-CD40 plus IL-4 resulted in marked enhancement of the migration response to BCA-1, SLC, ELC and SDF-1, reaching 30-60% migrated cells at 12 or 36 h of culture respectively. The activation-dependent increase in the migration efficacy was transient and declined to base level responses after 72 h of culture. Under no circumstances did we detect B lymphocyte chemotaxis to inflammatory chemokines. Also, mobilization of intracellular calcium ([Ca2+]l), an otherwise typical response of leukocytes to chemokines, was not observed. The transient increase in B lymphocyte migration did not correlate with changes in chemokine receptor expression, as evidenced by cell surface staining with antibodies to CXCR4, CXCR5 and CCR6, and by receptor transcript analyses. BCA-1, SLC, ELC and SDF-1 are typical 'housekeeping' chemokines with prominent expression at discrete locations in lymphoid tissues. Modulation of migration to these chemokines may be a critical mechanism for the proper positioning of B lymphocytes during humoral responses in secondary lymphoid tissues.