Toggle Main Menu Toggle Search

Open Access padlockePrints

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

Lookup NU author(s): Professor Kevin Marchbank

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


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.


Publication metadata

Author(s): Kulik L, Marchbank KJ, Lyubchenko T, Kuhn KA, Liubchenko GA, Haluszczak C, Gipson MG, Boackle SA, Holers VM

Publication type: Article

Publication status: Published

Journal: European Journal of Immunology

Year: 2007

Volume: 37

Issue: 3

Pages: 623-633

ISSN (print): 0014-2980

ISSN (electronic): 1521-4141

Publisher: Wiley - VCH Verlag GmbH & Co. KGaA

URL: http://dx.doi.org/10.1002/eji.200636248

DOI: 10.1002/eji.200636248

Notes: Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't


Altmetrics

Altmetrics provided by Altmetric


Actions

Find at Newcastle University icon    Link to this publication


Share