B cell-specific deletion of protein-tyrosine phosphatase Shp1 promotes B-1a cell development and causes systemic autoimmunity

Pao LI, Lam KP, Henderson JM, Kutok JL, Alimzhanov M, Nitschke L, Thomas ML, Neel BG, Rajewsky K (2007)

Publication Status: Published

Publication Type: Journal article

Publication year: 2007

Journal

Immunity Elsevier

Publisher: CELL PRESS

Book Volume: 27

Pages Range: 35-48

Journal Issue: 1

DOI: 10.1016/j.immuni.2007.04.016

Abstract

Spontaneous loss-of-function mutations in the protein-tyrosine phosphatase Shp1 cause the motheaten phenotype, characterized by widespread inflammation and autoimmunity. Because Shp1 is expressed in all hematopoietic cells, it has been unclear which aspects of the motheaten phenotypes are primary effects of Shp1 deficiency. We generated mice (Ptpn6(f/f), CD19-cre) that delete Shpl specifically in B cells. Analysis of these mice indicates that the increase in B-1a cells in motheaten mice is a cell-autonomous consequence of Shpl deficiency. Shp1-deficient B-1a cells could be derived from adult bone marrow and had N-nucleotide additions, consistent with an adult origin. Shpl1 deficiency altered calcium response evoked by B cell antigen receptors and impaired CD40-evoked proliferation. Young Ptpn6(f/f),-CD19-cre mice exhibited elevated serum immunoglobulins and impaired antibody responses to immunization, whereas older Ptpn6(f/f)-CD19-cre mice developed systemic autoimmunity, characterized by DNA antibodies and immune complex glomerulonephritis. Thus, Shpl deficiency in B cells alone perturbs B cell development and causes autoimmune disease.

Authors with CRIS profile

Lars Nitschke Professur für Genetik

Involved external institutions

Max-Delbrück-Centrum für Molekulare Medizin / Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch DE Germany (DE)

How to cite

APA:

Pao, L.I., Lam, K.-P., Henderson, J.M., Kutok, J.L., Alimzhanov, M., Nitschke, L.,... Rajewsky, K. (2007). B cell-specific deletion of protein-tyrosine phosphatase Shp1 promotes B-1a cell development and causes systemic autoimmunity. Immunity, 27(1), 35-48. https://doi.org/10.1016/j.immuni.2007.04.016

MLA:

Pao, Lily I, et al. "B cell-specific deletion of protein-tyrosine phosphatase Shp1 promotes B-1a cell development and causes systemic autoimmunity." Immunity 27.1 (2007): 35-48.

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