sIgD^- and sIgD⁺ B cells responding to thymus-independent antigens have a different lymphokine requirement

The discovery of the co-expression of cell surface IgM (sIgM) and sIgD on mature B lymphocytes (1) has led to speculations concerning the role of these two receptors in B cell activation (2). Several approaches have been used to examine the requirement for sIgM and/or sIgD in responses to thymus-independent (TI)⁴ and thymus-dependent antigens (3-11). However, these results have led to considerable controversy on the role of sIgD (3-11). One aspect of the controversy concerns the ability of sIgD^- (or μ predominant) B cells to respond to TI antigens. Buck et al. (9) suggested that sIgD^- B cells could not respond to TI antigens. However, they studied B cells from adult mice that contain few sIgD^- B cells. Because sIgD appears later than sIgM in ontogeny (6), Layton et al. (10) used B cell populations from neonatal mice (that contained about 50% sIgD^- B cells) to demonstrate that sIgD^- B cells could respond to TI antigens. This observation was confirmed by Marshall-Clarke et al. (12) but not by McFadden and Vitetta (13). The purpose of this study was to determine why Layton et al. (10) and McFadden and Vitetta (13) reached opposite conclusions when using very similar experimental approaches. In this regard, the variables in both systems were considered and a study was designed to test the role of at least one variable that could explain the discrepant results. This study shows that sIgD^- B cells respond well in limiting dilution cultures containing thymus filler cells, but respond poorly in cultures containing irradiated splenic filler cells. In contrast, sIgD⁺ B cells respond well in cultures containing either type of filler cell. The failure of irradiated splenic cells to support the responses of sIgD^- cells could be overcome by adding a source of T cell-derived lymphokines. It thus appears that sIgD^- cells can be triggered by TI antigens, but that triggering may require the presence of a lymphokine secreted by thymus cells but not by spleen cells. In contrast, sIgD⁺ cells can be triggered in the absence of this lymphokine.