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

Abstract：

: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.

journal_name

Blood

journal_title

Blood

authors

Wong SC,Oh E,Ng CH,Lam KP

doi

10.1182/blood-2002-08-2416

subject

Has Abstract

pub_date

2003-08-15 00:00:00

pages

1381-8

issue

4

eissn

0006-4971

issn

1528-0020

pii

2002-08-2416

journal_volume

102

pub_type

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