Critical Roles For the Bcl-3 Oncoprotein in T Cell-Mediated Immunity, Splenic Microarchitecture, and Germinal Center Reactions

Author:

Franzoso, G.

Carlson, L.

Schartonkersten, T.

Shores, E. W.

Epstein, S.

Grinberg, A.

Tran, T.

Shacter, E.

Leonardi, A.

Anver, M.

Love, P.

Sher, A.

Siebenlist, U.
Author Address

Siebenlist U NIAID IMMUNOREGULAT LAB NIH BLDG 10 BETHESDA, MD 20892 USA NIAID IMMUNOREGULAT LAB NIH BETHESDA, MD 20892 USA NIAID PARASIT DIS LAB NIH BETHESDA, MD 20892 USA NICHHD MOL GENET LAB NIH BETHESDA, MD 20892 USA US FDA CTR BIOL EVALUAT & RES DIV CELLULAR & GENE THERAPIES BETHESDA, MD 20892 USA SCI APPLICAT INT CORP PATHOL HISTOTECHNOL LAB FREDERICK, MD 21702 USA NCI FREDERICK CANC RES & DEV CTR FREDERICK, MD 21702 USA

Abstract:

Chromosomal translocations of bcl-3 are associated with chronic B cell lymphocytic leukemias. Previously, we have shown that Bcl-3, a distinct member of the I kappa B family, may function as a positive regulator of NF-kappa B activity, although its physiologic roles remained unknown. To uncover these roles, we generated Bcl-3-deficient mice. Mutant mice, but not their littermate controls, succumb to T. gondii owing to failure to mount a protective T helper 1 immune response. Bcl-3-deficient mice are also impaired in germinal center reactions and T-dependent antibody responses to influenza virus. The results reveal critical roles for Bcl-3 in antigen-specific priming of T and B cells. Altered microarchitecture of secondary lymphoid organs in mutant mice, including partial loss of B cells, may underlie the immunologic defects. The implied role of Bcl-3 in maintaining B cells in wild-type mice may related to its oncogenic potential. [References: 69]

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