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¹ Department of Pathology and Laboratory Medicine and ² Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322
³ Georgia Research Alliance, Atlanta, GA 30303
⁴ Emory Center for AIDS Research, Rollins School of Public Health, Emory University, Atlanta, GA 30322
⁵ Immunogenomics Group and ⁶ Laboratory for Immune Diversity, RIKEN Center for Allergy and Immunology, Tsurumi-ku, Yokohama City, Kanagawa 230-0045, Japan

CORRESPONDENCE Max D. Cooper: Max.Cooper{at}emory.edu

Morphologically and functionally distinct subpopulations of human memory B (B_Mem) cells are identifiable by either their expression of CD27 or Fc receptor–like 4 (FCRL4), an immunoglobulin domain containing a receptor with strong inhibitory potential. We have conducted comparative transcriptome and proteome analyses of FCRL4⁺ and FCRL4^– B_Mem cells and found that these two subsets have very distinctive expression profiles for genes encoding transcription factors, cell-surface proteins, intracellular signaling molecules, and modifiers of the cell-cycle status. Among the differentially expressed transcription factors, runt-related transcription factor 1 (RUNX1) transcript levels were up-regulated in FCRL4^– cells, whereas RUNX2 transcripts were preferentially detected in FCRL4⁺ cells. In vitro evidence for FCRL4 promoter responsiveness and in vivo promoter occupancy suggested that RUNX transcription factors are involved in the generation of these B_Mem cell subpopulations. A distinctive signature profile was defined for the FCRL4⁺ B_Mem cells by their expression of CD11c, receptor activator for nuclear factor B ligand, and FAS cell-surface proteins, in combination with increased levels of SOX5, RUNX2, DLL1, and AICDA expression. We conclude that this recently identified subpopulation of B_Mem cells, which normally resides in epithelial tissue-based niches, may serve a unique role in mucosal defense and, conversely, as a target for neoplastic transformation events.

Abbreviations used: AICDA, activation-induced cytidine deaminase; B_Mem, memory B; CBFβ, core-binding factor β; ChIP, chromatin immunoprecipitation; DLL1, delta-like 1; FCRL, Fc receptor like; GC, germinal center; HCK, hemopoietic cell kinase; LCK, lymphocyte-specific protein tyrosine kinase; RANKL, receptor activator for NF-B ligand; RUNX, runt-related transcription factor; SHP, Src homology 2 domain–containing phosphatase; SOX5, SRY-box 5; XBP1, X-box binding protein 1.

© 2008 Ehrhardt et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

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