I would like to bring to your attention a major weakness that I see with one of the studies you published. The study is that by Yan et al. “Identification of a receptor for BLyS demonstrates a crucial role in humoral immunity”1. My criticism is as follows.

The authors identify an orphan TNF receptor homolog as the receptor for the cytokine BLyS and demonstrate that blockade of receptor-BLyS interaction will inhibit the production of IgM and IgG1 secretion in vivo following antigen administration. The authors conclude from these data that BLyS “is essential for formation of splenic germinal centers” (last paragraph, page 37).

In my opinion the data shown in this manuscript are too preliminary to allow such conclusion to be drawn. A number of studies on mice deficient in secreted IgM have clearly demonstrated that secretion of IgM is essential for optimal induction of germinal center reactions and IgG production after antigen encounter2,3,4. Furthermore, it has been demonstrated that the lack of secreted IgM causes inefficient germinal center formation2. Therefore an alternative interpretation of the data generated by Yan et al., and one which is consistent with these previous reports, is that BLyS does not affect germinal center formation and affinity maturation. Instead, BLyS simply inhibits B cell activation and IgM secretion. The subsequent events, lack of germinal center formation and affinity maturation might be simply a consequence of the lack of secreted IgM. The finding that inhibition of the BLyS-receptor interaction affects IgM secretion much more than IgG secretion (see Fig. 5 in Yan et al.) supports such alternative interpretation.