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MR Vol.11 No.1 indexに戻る
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MODERN RHEUMATOLOGY
Vol.11 No.1 |
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Transcriptional regulation of memory
B cell development
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| T. Tokuhisa1, M. Hatano1, S. Okada1,
T. Fukuda1, I. Kunimasa1 |
| (1)Department of Developmental Genetics, Chiba
University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku,
Chiba 260-8670, Japan |
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| Abstract |
| Abstract Antigen-reactive B cells in the spleen
of mice immunized with T cell-dependent antigens generate antibody-producing
foci in periarteriolar lymphoid sheaths (PALS) or migrate into
follicles to form germinal centers. Germinal center B cells clonally
expand, have somatic hypermutation in IgV-region genes, are selected
by apoptosis on the basis of antigen-specific signals, and differentiate
to memory B cells. Two transcription factors (Bcl6 and c-Fos) in
B cells play a critical role in the development of germinal centers.
(1) Bcl6 is highly expressed in germinal center B cells, and defects
in B cells perturb the formation of germinal centers but not that
of PALS-associated foci, indicating the essential role of Bcl6
in the differentiation. (2) Overexpression of c-Fos in germinal
center B cells induces apoptosis and perturbs the formation of
memory B cells. Overexpression of Bcl-2 cannot rescue c-Fos-induced
apoptosis in germinal center B cells. Since c-Fos is induced in
mature B cells which have reacted with antigens, and clonal deletion
of self-reactive B cells is insensitive to overexpression of Bcl-2,
c-Fos may play a causal role in the clonal deletion of germinal
center B cells. Thus, these factors provide a unique opportunity
to investigate the molecular mechanisms of memory B cell development. |
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| Key words |
| Key words Bcl6 ・ c-Fos ・ Germinal center ・
Memory B cells |
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