Role of the receptor-like protein tyrosine phosphatase CD148 in the T cell-independent antibody response (109.12)

Abstract

Abstract Efficient elimination of a pathogen is dependent on both rapid and sustained antibody production by B cells. In contrast with conventional (B2) B cells, which produce antigen-specific antibody later in infection, B1 B cells generate natural antibodies and contribute to the T-cell independent (TI) antibody response. B cell activation and subsequent antibody secretion involve tyrosine phosphorylation, which is tightly regulated by protein tyrosine kinases (PTKs) and receptor-like protein tyrosine phosphatases (RPTPs). Previous studies from our lab have demonstrated that the RPTPs CD148 and CD45 have redundant positive regulatory roles in the development and antigen receptor signaling of B2 B cells by acting on on Src PTKs. However, the role of RPTPs in signal transduction in B1 B cells is not well understood. We have found that mice with a targeted deletion of the transmembrane domain of CD148 have an impaired IgM response when challenged with a TI antigen. This suggests that CD148 has a unique role in the TI response that cannot be compensated by CD45. Here, we use the mb1-cre transgenic mouse model as well as adoptive transfer experiments and in vitro analysis of B cell activation to characterize the function and specificity of CD148 in the B1 B cell response to TI antigen. These studies describe a previously unappreciated cell-autonomous role for CD148 in modulating signaling pathways that are important for the generation of TI antibody responses by B1 B cells.