1. The Calcineurin Phosphatase Complex Modulates Immunogenic B Cell Responses
- Author
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Winslow, Monte M., Gallo, Elena M., Neilson, Joel R., and Crabtree, Gerald R.
- Subjects
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B cells , *PLASMA cells , *IMMUNOGLOBULINS , *CYTOLOGICAL research , *MICE genetics - Abstract
Summary: A series of signal-directed transitions regulates the development of distinct populations of self-tolerant B cells and ultimately the production of antibody-producing plasma cells. We studied the role of calcineurin/NFAT signaling in B cells by deleting the regulatory b1 subunit of calcineurin specifically in B cells. Follicular (FO) and marginal zone (MZ) B cells develop normally in these mice, but B1 cell numbers are reduced. In vitro, calcineurin b1-deficient B cells have a cell-intrinsic proliferation defect downstream of the B cell receptor. These mice have higher total serum IgM despite the absence of B1 cells and have enhanced T cell-independent-1 responses. Conversely, mice with calcineurin b1-deficient B cells develop larger germinal centers and have reduced plasma cell development and antigen-specific antibody production during T cell-dependent immune responses. By several different criteria, calcineurin is dispensable for B cell tolerance, indicating that this phosphatase complex modulates immunogenic, but not tolerogenic, responses in vivo. [Copyright &y& Elsevier]
- Published
- 2006
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