RECOMBINANT TUMOR-NECROSIS-FACTOR ENHANCES THE LOCOMOTION OF MEMORY AND NAIVE B-LYMPHOCYTES FROM HUMAN TONSILS THROUGH THE SELECTIVE ENGAGEMENT OF THE TYPE-II RECEPTOR

Recent studies performed in mice knocked out for the tumor necrosis fa ctor (TNF), the lymphotoxin-alpha, or the type I TNF receptor (R), gen es have shown that these animals display gross defects in germinal cen ter (GC) formation, suggesting that members of the TNF and TNFR superf amilies are involved in the control of B-cell migration. Based on thes e premises, we have here investigated the effects of human recombinant (r) TNF on the polarization and locomotion of tonsillar B cells. rTNF increased the spontaneous polarization and locomotion of unfractionat ed tonsillar B lymphocytes in a hose-dependent manner by inducing a tr ue chemotactic response. Memory (IgD(-), CD38(-)) and naive (IgD(+), C D38(-)), but not GC (IgD(-), CD38(+)) B cells purified from total tons illar B lymphocytes, showed a significantly higher locomotion in the p resence than in the absence of rTNF. Accordingly, type I and II TNF re ceptors (TNFRs) were detected by flow cytometry on the surface of memo ry and naive, but not GC, B lymphocytes. Blocking experiments with mon oclonal antibodies to type I or II TNFR showed that rTNF enhanced the spontaneous chemotaxis of memory and naive B cells through the selecti ve engagement of type II TNFR. Finally, the TNF gene was found to be e xpressed in memory, naive and GC B lymphocytes; the cytokine was relea sed in culture supernatants from the three B-cell subsets after stimul ation. These data may support the hypothesis that human TNF is involve d in the paracrine and perhaps autocrine control of B-cell migration i n secondary lymphoid tissues. (C) 1997 by The American Society of Hema tology.