Repression of the Transcription Factor Bach2 Contributes to Predisposition of IgG1 Memory B Cells toward Plasma Cell Differentiation

Memory B cells are essential for generating rapid and robust secondary antibody responses. It has been thought that the unique cytoplasmic domain of IgG causes the prompt activation of antigen-experienced IgG memory B cells. To assess this model, we have generated a mouse containing IgG1 B cells tha...

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Published in	Immunity (Cambridge, Mass.) Vol. 39; no. 1; pp. 136 - 147
Main Authors	Kometani, Kohei, Nakagawa, Rinako, Shinnakasu, Ryo, Kaji, Tomohiro, Rybouchkin, Andrei, Moriyama, Saya, Furukawa, Koji, Koseki, Haruhiko, Takemori, Toshitada, Kurosaki, Tomohiro
Format	Journal Article
Language	English
Published	United States Elsevier Inc 25.07.2013 Elsevier Limited
Subjects	Animals Antigens B-Lymphocytes - immunology B-Lymphocytes - metabolism Basic-Leucine Zipper Transcription Factors - genetics Basic-Leucine Zipper Transcription Factors - immunology Basic-Leucine Zipper Transcription Factors - metabolism Cell Differentiation - genetics Cell Differentiation - immunology Cells, Cultured Flow Cytometry Gene Expression - immunology Immune system Immunoglobulin G - immunology Immunoglobulin G - metabolism Immunoglobulins Immunologic Memory - immunology Medical research Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Mice, Transgenic PAX5 Transcription Factor - genetics PAX5 Transcription Factor - immunology PAX5 Transcription Factor - metabolism Plasma Cells - immunology Plasma Cells - metabolism Reverse Transcriptase Polymerase Chain Reaction RNA Interference TOR Serine-Threonine Kinases - immunology TOR Serine-Threonine Kinases - metabolism
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Abstract	Memory B cells are essential for generating rapid and robust secondary antibody responses. It has been thought that the unique cytoplasmic domain of IgG causes the prompt activation of antigen-experienced IgG memory B cells. To assess this model, we have generated a mouse containing IgG1 B cells that have never encountered antigen. We found that, upon challenge, antigen-experienced IgG1 memory B cells rapidly differentiated into plasma cells, whereas nonexperienced IgG1 B cells did not, suggesting the importance of the stimulation history. In addition, our results suggest that repression of the Bach2 transcription factor, which results from antigen experience, contributes to predisposition of IgG1 memory B cells to differentiate into plasma cells. •IgG1 tail alone cannot explain robust antibody production•Expression of Bach2 is decreased in IgG1 memory B cells•Repression of Bach2 contributes to robust antibody production•mTOR signaling is involved in Bach2 repression
AbstractList	Memory B cells are essential for generating rapid and robust secondary antibody responses. It has been thought that the unique cytoplasmic domain of IgG causes the prompt activation of antigen-experienced IgG memory B cells. To assess this model, we have generated a mouse containing IgG1 B cells that have never encountered antigen. We found that, upon challenge, antigen-experienced IgG1 memory B cells rapidly differentiated into plasma cells, whereas nonexperienced IgG1 B cells did not, suggesting the importance of the stimulation history. In addition, our results suggest that repression of the Bach2 transcription factor, which results from antigen experience, contributes to predisposition of IgG1 memory B cells to differentiate into plasma cells. Memory B cells are essential for generating rapid and robust secondary antibody responses. It has been thought that the unique cytoplasmic domain of IgG causes the prompt activation of antigen-experienced IgG memory B cells. To assess this model, we have generated a mouse containing IgG1 B cells that have never encountered antigen. We found that, upon challenge, antigen-experienced IgG1 memory B cells rapidly differentiated into plasma cells, whereas nonexperienced IgG1 B cells did not, suggesting the importance of the stimulation history. In addition, our results suggest that repression of the Bach2 transcription factor, which results from antigen experience, contributes to predisposition of IgG1 memory B cells to differentiate into plasma cells.Memory B cells are essential for generating rapid and robust secondary antibody responses. It has been thought that the unique cytoplasmic domain of IgG causes the prompt activation of antigen-experienced IgG memory B cells. To assess this model, we have generated a mouse containing IgG1 B cells that have never encountered antigen. We found that, upon challenge, antigen-experienced IgG1 memory B cells rapidly differentiated into plasma cells, whereas nonexperienced IgG1 B cells did not, suggesting the importance of the stimulation history. In addition, our results suggest that repression of the Bach2 transcription factor, which results from antigen experience, contributes to predisposition of IgG1 memory B cells to differentiate into plasma cells. Memory B cells are essential for generating rapid and robust secondary antibody responses. It has been thought that the unique cytoplasmic domain of IgG causes the prompt activation of antigen-experienced IgG memory B cells. To assess this model, we have generated a mouse containing IgG1 B cells that have never encountered antigen. We found that, upon challenge, antigen-experienced IgG1 memory B cells rapidly differentiated into plasma cells, whereas nonexperienced IgG1 B cells did not, suggesting the importance of the stimulation history. In addition, our results suggest that repression of the Bach2 transcription factor, which results from antigen experience, contributes to predisposition of IgG1 memory B cells to differentiate into plasma cells. •IgG1 tail alone cannot explain robust antibody production•Expression of Bach2 is decreased in IgG1 memory B cells•Repression of Bach2 contributes to robust antibody production•mTOR signaling is involved in Bach2 repression
Author	Moriyama, Saya Koseki, Haruhiko Takemori, Toshitada Furukawa, Koji Kaji, Tomohiro Nakagawa, Rinako Shinnakasu, Ryo Kometani, Kohei Rybouchkin, Andrei Kurosaki, Tomohiro
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Snippet	Memory B cells are essential for generating rapid and robust secondary antibody responses. It has been thought that the unique cytoplasmic domain of IgG causes...
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SubjectTerms	Animals Antigens B-Lymphocytes - immunology B-Lymphocytes - metabolism Basic-Leucine Zipper Transcription Factors - genetics Basic-Leucine Zipper Transcription Factors - immunology Basic-Leucine Zipper Transcription Factors - metabolism Cell Differentiation - genetics Cell Differentiation - immunology Cells, Cultured Flow Cytometry Gene Expression - immunology Immune system Immunoglobulin G - immunology Immunoglobulin G - metabolism Immunoglobulins Immunologic Memory - immunology Medical research Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Mice, Transgenic PAX5 Transcription Factor - genetics PAX5 Transcription Factor - immunology PAX5 Transcription Factor - metabolism Plasma Cells - immunology Plasma Cells - metabolism Reverse Transcriptase Polymerase Chain Reaction RNA Interference TOR Serine-Threonine Kinases - immunology TOR Serine-Threonine Kinases - metabolism
Title	Repression of the Transcription Factor Bach2 Contributes to Predisposition of IgG1 Memory B Cells toward Plasma Cell Differentiation
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