Responsiveness of B cells is regulated by the hinge region of IgD.
06.04.2015 Übelhart R, Hug E, Bach MP, Wossning T, Dühren-von Minden M, Horn AH, Tsiantoulas D, Kometani K, Kurosaki T, Binder CJ, Sticht H, Nitschke L, Reth M, Jumaa H. Nat Immunol. 2015;16(5):534-43. Mature B cells express two classes B cell antigen receptor (BCR) namely the IgM-BCR and the IgD-BCR. The different signaling functions of these two receptors have been unclear. By using a cellular in vitro system and corresponding mouse models, we found that antigens with low valence activated the IgM-BCR but failed to trigger the IgD-BCR signaling, whereas polyvalent antigens activated both receptor classes. Investigations of the molecular mechanism showed that deletion of the IgD-specific hinge region rendered the IgD-BCR responsive to monovalent antigen, whereas transferring the hinge to IgM resulted in responsiveness only to polyvalent antigen. Our data suggest that the increased IgD/IgM ratio on conventional B-2 cells is important for preferential immune responses to antigens in immune complexes, and that the increased IgM expression on B-1 cells is essential for B-1 cell homeostasis and function. 