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From the Department of Immunobiology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, California 94304

Memory B cells isolated from human tonsils are characterized by an activated cell surface phenotype, localization to mucosal epithelium, expression of somatically mutated immunoglobulin (Ig) variable (V) region genes, and a preferential differentiation into plasma cells in vitro. In spleens of both humans and rodents, a subset of memory B cells is believed to reside in the marginal zone of the white pulp. Similar to tonsil-derived memory B cells, splenic marginal zone B cells can be distinguished from naive follicular B cells by a distinct cell surface phenotype and by the presence of somatic mutations in their Ig V region genes. Although differences exist between human naive and memory B cells, no cell surface molecules have been identified that positively identify all memory B cells. In this study, we have examined the expression of the receptor-type protein tyrosine phosphatase CD148 on human B cells. CD148⁺ B cells present in human spleen exhibited characteristics typical of memory B cells. These included an activated phenotype, localization to the marginal zone, the expression of somatically mutated Ig V region genes, and the preferential differentiation into plasma cells. In contrast, CD148^– B cells appeared to be naive B cells due to localization to the mantle zone, the expression of surface antigens typical of unstimulated B cells, and the expression of unmutated Ig V region genes. Interestingly, CD148⁺ B cells also coexpressed CD27, whereas CD148^– B cells were CD27^–. These results identify CD148 and CD27 as markers which positively identify memory B cells present in human spleen. Thus, assessing expression of these molecules may be a convenient way to monitor the development of memory B cell responses in immunocompromised individuals or in vaccine trials.

Key Words: human memory B cells • marginal zone B cells • somatic mutation • CD148 • CD27

This paper is dedicated to Bruce F. Bennett, a dear friend and colleague of everyone at DNAX.

DNAX Research Institute is supported by the Schering-Plough Corporation.

G. Aversa and J. de Vries's current address is Novartis Research Institute, Brunner Strasse 59, A-1235 Vienna, Austria.

Abbreviations used: FR, framework region(s); FSC, forward angle light scatter; GC, germinal center(s); MFI, mean fluorescence intensity; MNC, mononuclear cell(s); SSC, side scatter; SAC, Staphylococcus aureus Cowan; SLAM, signaling lymphocytic activation molecule.

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