The Journal of Experimental Medicine
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Published online
doi:10.1084/jem.20062104
The Journal of Experimental Medicine, Vol. 204, No. 4, 819-830
The Rockefeller University Press, 0022-1007 $30.00
© Kuo et al.
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ARTICLE

 Repression of BCL-6 is required for the formation of human memory B cells in vitro

Tracy C. Kuo1, Arthur L. Shaffer2, Joseph Haddad, Jr.3, Yong Sung Choi4, Louis M. Staudt2, and Kathryn Calame1,5

1 Department of Microbiology, Columbia University Medical Center, New York, NY 10032
2 Metabolism Branch, Center for Cancer Research, National Cancer Institute Bethesda, MD 20892
3 Division of Pediatric Otolaryngology, Columbia University Medical Center, New York, NY 10032
4 Laboratory of Cellular Immunology, Ochsner Clinic Foundation, New Orleans, LA 70121
5 Department of Biochemistry and Molecular Biophysics, Columbia University Medical Center, New York, NY 10032

CORRESPONDENCE Kathryn Calame: klc1{at}columbia.edu

Memory B cells provide rapid protection to previously encountered antigens; however, how these cells develop from germinal center B cells is not well understood. A previously described in vitro culture system using human tonsillar germinal center B cells was used to study the transcriptional changes that occur during differentiation of human memory B cells. Kinetic studies monitoring the expression levels of several known late B cell transcription factors revealed that BCL-6 is not expressed in memory B cells generated in vitro, and gene expression profiling studies confirmed that BCL-6 is not expressed in these memory B cells. Furthermore, ectopic expression of BCL-6 in human B cell cultures resulted in formation of fewer memory B cells. In addition, the expression profile of in vitro memory B cells showed a unique pattern that includes expression of genes encoding multiple costimulatory molecules and cytokine receptors, antiapoptotic proteins, T cell chemokines, and transcription factors. These studies establish new molecular criteria for defining the memory B cell stage in human B cells.

Abbreviations used: 7-AAD, 7-amino actinomycin D; AID, activation-induced cytidine deaminase; BCMA, B cell maturation antigen; BCR, B cell receptor; GC, germinal center.


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