Notch-RBP-J-independent marginal zone B cell development in IgH transgenic mice with VH derived from a natural polyreactive antibody.

Abstract

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.