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Prepublished online as a Blood First Edition Paper on April 24, 2003; DOI 10.1182/blood-2002-08-2416.

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2002-08-2416v1
102/4/1381    most recent
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Blood, 15 August 2003, Vol. 102, No. 4, pp. 1381-1388

IMMUNOBIOLOGY

Impaired germinal center formation and recall T-cell–dependent immune responses in mice lacking the costimulatory ligand B7-H2

Siew-Cheng Wong, Edwin Oh, Chee-Hoe Ng, and Kong-Peng Lam

From the Institute of Molecular and Cell Biology (IMCB), Singapore.

B7-H2, which is expressed constitutively on B cells and binds the inducible costimulator (ICOS) on antigen-activated T cells, is a member of the B7 family of costimulatory ligands. We have inactivated B7-H2 in the mouse. B7-H2/ mice generate normal populations of B and T cells in their various lymphoid organs but have lower basal levels of heavy chain class–switched antibodies in their sera. These mice are able to mount normal immune responses to both type I and type II T-cell–independent antigens. However, their pattern of responses to a T-cell–dependent antigen is altered, with greatly reduced production of antigen-specific heavy chain class–switched antibodies, the levels of which could not be elevated even with repeated immunizations. This suggests a critical role for B7-H2 in the recall phases of the immune response. Germinal center formation is also impaired in the mutant mice. While B cells from the mutant mice could response normally to anti-IgM, anti-CD40, and lipopolysaccharide stimulation, the production of T-helper–type II cytokines such as interleukin-4 (IL-4) and IL-10 by primed CD4+ T cells from mutant mice were reduced. This indicated that the defects in humoral responses and germinal center formation in B7-H2–deficient mice are due to the lack of T-cell–mediated help to the B cells. Hence, B7-H2 on B cells is important for recruiting T-cell help via its interaction with ICOS and plays a critical role in costimulating humoral immune responses.


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