Macrophage- and dendritic cell--dependent regulation of XXXX B-cell proliferation requires the TNF family ligand @entity8410 .

@entity1 @entity7430 @entity48890 @entity8410 @entity2936 @entity25128 @entity32969 @entity6469
Macrophages and dendritic cells play an important role in regulating B-cell responses, including proliferation to antigens such as @entity7430 (TNP)-Ficoll and TNP- @entity6469 . However, the mechanisms and molecule(s) that regulate these processes are relatively undefined. In this report, we show that @entity1 macrophages generated in vitro strongly costimulate proliferation of dense @entity1 tonsillar B cells ligated via their @entity25128 ( @entity25128 ) but not proliferation via @entity2936 . Similarly, dendritic cells also markedly enhance @entity25128 -activated B-cell proliferation. Soluble molecule(s) are required for @entity1 macrophages to costimulate proliferation of B cells triggered via their @entity25128 . Importantly, a TACI (trans-membrane activator and @entity48890 interactor)-Fc fusion protein inhibits both macrophage- and dendritic cell (DC)-dependent @entity25128 -activated B-cell proliferation, indicating a requirement for at least one of the known TACI ligands, @entity8410 and/or @entity32969 . Consistent with a major role for @entity8410 , macrophages release @entity8410 at levels sufficient to potently costimulate @entity25128 -induced B-cell proliferation. In addition, @entity8410 is more than 100-fold more potent than @entity32969 in enhancing @entity25128 -mediated @entity1 B-cell proliferation. Furthermore, immunodepletion of @entity32969 under conditions that prevent @entity32969 -mediated B-cell costimulation does not block macrophage enhancement of B-cell proliferation. Finally, there is no correlation between the high levels of @entity32969 ( @entity32969 ) expressed by macrophages compared with DCs and the similar abilities of macrophages and DCs to enhance @entity25128 -stimulated B-cell proliferation. In summary, our results suggest that macrophage- and DC-derived B-cell-activating factor belonging to the TNF family ( @entity8410 ) represents a key molecule by which macrophages and DCs directly regulate @entity1 B-cell proliferative responses to T-cell-independent stimuli.
