Generation of functional murine CD11c + age‐associated B cells in the absence of B cell T‐bet expression
Year: 2018
Type: article
Abstract: Age‐associated B cells (ABC), a novel subset of activated B cells defined by CD11b and CD11c expression, have been linked with both protective anti‐viral responses and the pathogenesis of systemic autoimmunity. Expression of the T H 1 lineage transcription factor T‐bet has been identified as a defining feature of ABC biology, with B cell‐intrinsic expression of this transcription factor proposed to be required for ABC formation. In contrast to this model, we report that Tbx21 (encoding T‐bet)‐deficient B cells upregulate CD11b and CD11c surface expression in vitro in response to integrated TLR and cytokine signals. Moreover, B cell‐intrinsic T‐bet deletion in a murine lupus model exerted no impact of ABC generation in vivo, with Tbx21 −/− ABCs exhibiting an identical surface phenotype to wild‐type (WT) ABCs. Importantly, WT and Tbx21 −/− ABCs sorted from autoimmune mice produced equivalent amounts of IgM and IgG ex vivo following TLR stimulation, indicating that T‐bet‐deficient ABCs are likely functional in vivo. In summary, our data contradict the established literature by demonstrating that T‐bet expression is not uniformly required for ABC generation.
Source: European Journal of Immunology
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
Funders: American College of Rheumatology Research and Education Foundation, Arthritis National Research Foundation, Lupus Research Institute, Rheumatology Research Foundation, Seattle Children's Research Institute, Children’s Hospital of Wisconsin Research Institute, Lupus Research Alliance, National Research Foundation, National Institutes of Health, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: B cell-intrinsic cytokine regulation and B cell-targeted therapies in murine lupu, Defining the functional impact of T1D genes in mouse and man: a unified strategy, Lentiviral Gene Therapy of X-Linked Agammaglobulinemia, Mechanisms underlying TACI-dependent activation of immature transitional B cells in BAFF-driven humoral autoimmunity, An integrated strategy to define the functional and synergistic impact of T1D causal variants, Lentiviral Gene Therapy for Wiskott-Aldrich Syndrome
OpenAlex ID: W2898365748