B cell development and immunoglobulin production are altered in the absence of IκBNS (109.4)

Abstract

Abstract NF-κB transcription factors are key mediators of immune function as well as inflammatory responses. The activation of NF-κB is regulated by several IκB proteins, a family comprising classical cytoplasmic as well as nuclear IκBs. In this study, we focused on the role of IκBNS, a nuclear IκB protein, in B lymphocyte development and function. Analysis of lymphoid tissues from IκBNS knockout (KO) mice revealed that a lack of IκBNS affects the development of peritoneal B-1 cells and splenic marginal zone B cells. Development of B-2 cells was essentially normal. We also found that B cell proliferative activity and immunoglobulin production were altered in the absence of IκBNS. These defects were confirmed by the analysis of B cells in bone marrow chimeric mice constructed by the transfer of wild type or IκBNS KO bone marrow cells into B cell-deficient mice. Furthermore, histological analysis of spleens from chimeric mice revealed that re-constitution of B cell areas, marginal zones and germinal centers were markedly reduced in IκBNS KO cell recipient mice. Examination of the functions of IκBNS KO B cell subsets suggested that IκBNS is important for antibody production by both marginal zone and follicular B cells. These results indicate that IκBNS plays a key role in peripheral B cell development and function.