Differential requirement for OBF-1 during antibody-secreting cell differentiation
- Corcoran, LM; Hasbold, J; Dietrich, W; Hawkins, E; Kallies, A; Nutt, SL; Tarlinton, DM; Matthias, P; Hodgkin, PD;
Publication Year 2005-05-02, Volume 201, Issue #9, Page 1385-1396
- Journal Title
- JOURNAL OF EXPERIMENTAL MEDICINE
- Publication Type
- Journal Article
- Resting B cells can be cultured to induce antibody-secreting cell (ASC) differentiation in vitro. A quantitative analysis of cell behavior during such a culture allows the influences of different stimuli and gene products to be measured. The application of this analytical system revealed that the OBF-1 transcriptional coactivator, whose loss impairs antibody production in vivo, has two effects on ASC development. Although OBF-1 represses early T cell dependent (TD) differentiation, it is also critical for the completion of the final stages of ASC development. Under these conditions, the loss of OBF-1 blocks the genetic program of ASC differentiation so that Blimp-1/prdm1 induction fails, and bcl-6, Pax5, and AID are not repressed as in control ASC. Retroviral complementation confirmed that OBF-1 was the critical entity. Surprisingly, when cells were cultured in lipopolysaccharide to mimic T cell independent conditions, OBF-1-null B cells differentiated normally to ASC. In the OBF-1(-/-) ASC generated under either culture regimen, antibody production was normal or only modestly reduced, revealing that Ig genes are not directly dependent on OBF-1 for their expression. The differential requirement for OBF-1 in TD ASC generation was confirmed in vivo. These studies define a new regulatory role for OBF-1 in determining the cell-autonomous capacity of B cells to undergo terminal differentiation in response to different immunological signals.
- ROCKEFELLER UNIV PRESS
- DIACETATE SUCCINIMIDYL ESTER; TRANSCRIPTION FACTOR XBP-1; GERMINAL CENTER FORMATION; LYMPHOCYTE DIFFERENTIATION; B-CELLS; PLASMA-CELLS; BLIMP-1 EXPRESSION; STERNBERG CELLS; GENE-EXPRESSION; OCA-B
- Publisher's Version
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Creation Date: 2005-05-02 12:00:00Last Modified: 0001-01-01 12:00:00