Genetic loss of NFAT2 (NFATc1) impairs B cell development of B1 and B2 B cells

Highlights

• B cell specific NFAT2 deletion by CD19cre is a useful model for analyzing B cell development.

• NFAT2 activity is essential for normal B1 cell development.

• Loss of NFAT2 leads to increased immature transitional B cells and mature follicular B cells.

• Genetic deletion of NFAT2 increases B cell apoptosis and decreases proliferation capacity.

Abstract

NFAT2 activity was shown to be of critical importance in B cell receptor signaling, development and proliferation; however its role in B cell development in the periphery is still not completely understood. We confirmed that NFAT2 deletion leads to impaired B1 B cell development, supported by our finding of limited B1 progenitors in the bone marrow and spleen of NFAT2 deficient mice. Moreover, we show for the first time that loss of NFAT2 increases immature B cells in particular transitional T2 and T3 as well as mature follicular B cells while marginal zone B cells are decreased. We further demonstrate that NFAT2 regulates the expression of B220, CD23, CD38, IgM/IgD and ZAP70 in murine B cells. In vivo analyses revealed decreased proliferation and increased apoptosis of NFAT2 deficient B cells. In summary, this study provides an extensive analysis of the role of NFAT2 in peripheral B lymphocyte development.