Intrinsic B cell hypo-responsiveness in mice prematurely expressing human CR2/CD21 during B cell development.

Abstract

We previously reported that human CR2 (hCR2) prematurely expressed under a murine Vlambda2 promoter/Vlambda2-4 enhancer minigene during the CD43+ CD25- late pro-B cell stage of development results in peripheral B cells with impaired responses to immunization with T-dependent antigens. Herein, we show that hCR2 transgenic (Tg) mice also demonstrate a severe defect in T-independent antigen responses and are substantially protected from clinical arthritis, synovitis and cartilage/bone destruction in a collagen-induced arthritis model. This outcome is found despite the apparently normal development of autoreactive T cells with equivalent cytokine and proliferative responses to antigen when compared to non-Tg control mice. These data suggest the presence of an intrinsic B cell defect in the hCR2 Tg mice. We also show that an hCR2-dependent Ca2+ influx can be generated in both developing and mature Tg B cells, but with different rates of decay as compared to control wild-type (WT) mice. In addition, although analysis of tyrosine-phosphorylated proteins in WT and Tg B cells following B cell receptor (BCR)-induced activation revealed the presence of distinctly different phosphorylation patterns, no differences were identified in several candidate protein targets. Overall, these data suggest that premature hCR2 expression and the consequences thereof during B cell development intrinsically alters the way mature B cells develop and subsequently respond to antigen through the BCR signaling complex.

• Authors: Liudmila Kulik, Kevin J Marchbank, Taras Lyubchenko, Kristine A Kuhn, Ganna A Liubchenko, Catherine Haluszczak, Matthew G Gipson, Matthew G Gibson, Susan A Boackle, V Michael Holers
• Journal: European journal of immunology (Eur J Immunol) Vol. 37 Issue 3 Pg. 623-33 (Mar 2007) ISSN: 0014-2980 [Print] Germany
• PMID: 17301948 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Antigen, B-Cell
• Receptors, Complement 3d

Topics

• Animals
• Antibody Formation (genetics)
• Arthritis, Experimental (genetics, immunology)
• B-Lymphocytes (cytology, immunology, metabolism)
• Cell Differentiation (immunology)
• Humans
• Lymphocyte Activation (genetics)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Inbred DBA
• Mice, Transgenic
• Receptors, Antigen, B-Cell (physiology)
• Receptors, Complement 3d (biosynthesis, genetics, immunology)
• Signal Transduction (genetics, immunology)