Generation of a Batf null mouse: Using mouse genetics to map Batf expression and determine Batf function
Abstract
The AP-1 family of transcription factors have been implicated in processes of cell differentiation, proliferation, transformation and apoptosis. Because of its involvement in so many processes, AP-1 is a crucial regulator of many different cell types, including immune cells. AP-1 comprises a family of basic leucine zipper transcription factors known to dimerize and bind to specific sequences in DNA to affect transcription. Batf, an AP-1 factor, is expressed in murine B and T cells, and experiments performed in this study have shown that Batf is expressed in mouse testis. To investigate the function of Batf, a mouse was generated that is deficient in Batf (Batf ΔZ/ΔZ). These mice are fertile and show no obvious defects in testis architecture or function. As for the immune system, BatfΔZ/ΔZ mice possess normal numbers of B cells, but show reduced numbers of peripheral CD4+ T cells. Analysis of CD4+ T helper cell subsets in Batf ΔZ/ΔZ mice has demonstrated that Batf is required for the development of functional T helper 17 (Th17), Th2 and T follicular helper (Tfh) cells. The cytokines most commonly associated with these lineages, IL-17, IL-4, and IL-21, respectively, are all dramatically reduced in Batf-deficient mice. Interestingly, these cytokines have been shown to play important roles in the maturation of immunoglobulin-secreting B cells. Batf ΔZ/ΔZ mice display drastically reduced serum antibody. Upon antigen challenge, germinal centers do not develop in BatfΔZ/ΔZ mice. While adoptive transfer experiments confirmed that this B cell phenotype can be driven by defects in the BatfΔZ/ΔZ CD4+ T cell compartment, stimulation of BatfΔZ/ΔZ B cells in vitro, or by a T cell-independent antigen in vivo did not result in class-switch recombination (CSR). Based the observed phenotypes, it can be concluded that the loss of Batf disrupts multiple components of the lymphocyte communication network required for a robust humoral immune response.
Degree
Ph.D.
Advisors
Taparowsky, Purdue University.
Subject Area
Molecular biology|Immunology
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