The Journal of Experimental Medicine
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Published 2 May 2005. doi:10.1084/jem.20042325
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 201, Number 9, 1385-1396
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ARTICLE

 Differential requirement for OBF-1 during antibody-secreting cell differentiation

Lynn M. Corcoran1, Jhagvaral Hasbold1, Wendy Dietrich1, Edwin Hawkins1, Axel Kallies1, Stephen L. Nutt1, David M. Tarlinton1, Patrick Matthias2, and Philip D. Hodgkin1

1 The Walter and Eliza Hall Institute of Medical Research, Parkville Victoria 3050, Australia
2 Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland

CORRESPONDENCE Lynn M. Corcoran: corcoran{at}wehi.edu.au

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.

Abbreviations used: ASC, antibody-secreting cell; CFSE, carboxyfluorescein diacetate succinimidyl ester; GC, germinal center; TD, T cell–dependent.


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