Notch-RBP-J-Independent Marginal Zone B Cell Development in IgH Transgenic Mice with VH Derived from a Natural Polyreactive Antibody

Both the B cell antigen receptor (BCR) signaling and Notch signaling pathway play important roles in marginal zone (MZ) B cell development; however, if and how these two signaling pathways engage in crosstalk with each other remain unclear. In the present study, IgH transgenic mice (TgV H 3B4) were crossed with mice with Notch downstream transcription factor RBP-J floxed alleles (RBP-J f/f ) and Mx-Cre transgene. Subsequently, MZ B cell development was analyzed in 3B4/Cre/RBP-J f/f mice that expressed the transgenic 3B4 IgH and exhibited a deficiency in Notch signaling in B cells upon poly (I:C) injection. We observed that MZ B cell numbers were severely reduced, but still detectable in 3B4/Cre/RBP-J f/f mice, in contrast to increased numbers of MZ B cells in TgV H 3B4 mice and almost no MZ B cells in Cre/RBP-J f/f mice. The majority of the MZ B cells in the 3B4/Cre/RBP-J f/f mice had the same antigen specificity with that of 3B4 antibody, indicating that a particular BCR specificity might direct MZ B cell development in the absence of Notch signaling. The number of MZ B precursor (MZP) cells was reduced sharply in 3B4/Cre/RBP-J f/f mice, and the number of transitional stage 1 and transitional stage 2 cells did not change that much, indicating that the interaction between BCR and Notch signaling likely occurred during the T2-MZP stage. Based on the transgenic mouse model, our data indicate that MZ B cells with certain BCR specificity can develop in a Notch-RBP-J independent manner.