rC5a directs the in vitro migration of human memory and naive tonsillar B lymphocytes: Implications for B cell trafficking in secondary lymphoid tissues

Human C5a is a potent chemoattractant for granulocytes, monocytes, and dend ritic cells, In mice C5a has been shown. to be chemotactic for germinal cen ter (GC) B cells. To date, no information is available on the effects of C5 a on human B cell locomotion. Here we demonstrate that rC5a increases polar ization and migration of human tonsillar;B cells, The locomotory response w as due to both chemokinetic and chemotactic activities of rC5a, Moreover, m emory and-at a lesser extent, naive B cell fractions from purified tonsilla r populations displayed rC5a-enhanced migratory properties, whereas GC cell s did not. Flow cytometry revealed C5aR (CD88) on approximately 40% memory and 10% naive cells, respectively, whereas GC cells were negative. Immunohi stochemistry showed that a few CD88(+) cells were of the B cell lineage and localized in tonsillar subepithelial areas, where the majority of memory B cells settle. Pretreatment of memory B cells with the CD88 mAb abolished t heir migratory responsiveness to rC5a, Finally, the C5 gene was found to be expressed in naive, GC, and memory B lymphocytes at both the mRNA and the protein level, This study delineates a novel role for C5a as a regulator of the trafficking of human memory and naive Il lymphocytes and supports the hypothesis that the B cells themselves may serve as source of C5 in seconda ry lymphoid tissues.