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* Institute of Stem Cell Biology and Regenerative Medicine, Stanford Cancer Center, Stanford University School of Medicine, Stanford, CA 94305;
Osaka University Graduate School of Medicine, Department of Cancer Stem Cell Biology, Department of Respiratory Medicine, Allergy and Rheumatic Disease, Osaka, Japan;
Departments of Pediatrics and Physiology and Pharmacology, University of Western Ontario, Children’s Health Research Institute, London, Ontario, Canada; and
Division of Immunology, Cancer Research Laboratory, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720
Humoral immunity is characterized by the generation of Ab-secreting plasma cells and memory B cells that can more rapidly generate specific Abs upon Ag exposure than their naive counterparts. To determine the intrinsic differences that distinguish naive and memory B cells and to identify pathways that allow germinal center B cells to differentiate into memory B cells, we compared the transcriptional profiles of highly purified populations of these three cell types along with plasma cells isolated from mice immunized with a T-dependent Ag. The transcriptional profile of memory B cells is similar to that of naive B cells, yet displays several important differences, including increased expression of activation-induced deaminase and several antiapoptotic genes, chemotactic receptors, and costimulatory molecules. Retroviral expression of either Klf2 or Ski, two transcriptional regulators specifically enriched in memory B cells relative to their germinal center precursors, imparted a competitive advantage to Ag receptor and CD40-engaged B cells in vitro. These data suggest that humoral recall responses are more rapid than primary responses due to the expression of a unique transcriptional program by memory B cells that allows them to both be maintained at high frequencies and to detect and rapidly respond to antigenic re-exposure.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health Grant P01DK053074 (to I.L.W.). D.B. was supported by a fellowship from the Cancer Research Institute and from the National Institutes of Health (T32AI0729022), C.B.F. was supported by a predoctoral fellowship from the National Science Foundation, and N.H. was supported by a fellowship from the Japanese Society of Promotion of Science, Yamada Memorial Foundation, and Mitsubishi Pharma Research Foundation.
2 Address correspondence and reprint requests to Dr. Deepta Bhattacharya, B261 Beckman Center, 279 Campus Drive, Stanford, CA 94305-5323. E-mail address: deepta{at}stanford.edu
3 Abbreviations used in this paper: PNA, peanut agglutinin; AID, activation-induced deaminase; CGG, chicken 
-globulin; DAPI, 4',6-diamidino-2-phenylindole; IRES, internal ribosomal entry site; MSCV, murine stem cell virus; NP, hydroxy-3-nitrophenylacetyl; S1P1, sphingosine-1 phosphate receptor 1.
4 The on-line version of this article contains supplemental material.
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