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Defective B cell ontogeny and immune response in human complement receptor 2 (CR2, CD21) transgenic mice is partially recovered in the absence of C3

Lookup NU author(s): Professor Kevin Marchbank

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Abstract

Mice prematurely expressing human CR2 (hCR2) in the B cell lineage have a defective B cell ontogeny and immune response. Our recent analysis of this phenotype suggested that signaling through hCR2 and presumably mouse CD19 on the B cell surface, during bone marrow development, could result in the observed changes in B cell function in these mice. To test this hypothesis, we back crossed hCR2high transgenic mice onto the CD19-/- background. CD19-/-hCR2high mice were found to possess even fewer mature B cells than their CD19+/+hCR2high littermates, demonstrating that loss of CD19 exacerbated the effects elicited through hCR2. This data suggests that CD19 provides a survival signal during B cell development in this model. Next, we examined if the removal of the main ligand for CR2, namely C3d, through back-crossing onto the C3-/- background could restore normal B cell development. However, we found only minor recovery in peripheral B cell numbers and no obvious change in function. This was despite a three-fold increase in the level of hCR2 expression on B cells isolated from the spleen or bone marrow of C3-/-hCR2high mice when compared with C3 sufficient littermates. These data demonstrate that hCR2 is integrated in mouse B cell signaling and that the downstream effects of hCR2 expression during early B cell development are partially but not completely due to interaction with C3 fragments and signaling through CD19 in the bone marrow environment. © 2007 Elsevier Ltd. All rights reserved.


Publication metadata

Author(s): Twohig J, Kulik L, Haluszczak C, Reuter J, Rossbach A, Bull M, Holers VM, Marchbank KJ

Publication type: Article

Publication status: Published

Journal: Molecular Immunology

Year: 2007

Volume: 44

Issue: 13

Pages: 3434-3444

ISSN (print): 0161-5890

ISSN (electronic): 1872-9142

Publisher: Pergamon

URL: http://dx.doi.org/10.1016/j.molimm.2007.02.011

DOI: 10.1016/j.molimm.2007.02.011

PubMed id: 17379312


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