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¹ Division of Clinical and Developmental Immunology, University of Alabama at Birmingham, Birmingham, AL 35294
² Division of Hematology/Oncology, University of Alabama at Birmingham, Birmingham, AL 35294
³ Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294
⁴ Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL 35294
⁵ Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294
⁶ Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294
⁷ Howard Hughes Medical Institute, University of Alabama at Birmingham, Birmingham, AL 35294

CORRESPONDENCE Max D. Cooper: max.cooper{at}ccc.uab.edu

The FcRH4 transmembrane molecule, a member of the Fc receptor homologue family, can potently inhibit B cell receptor (BCR) signaling. We show that cell surface expression of this immunoregulatory molecule is restricted to a subpopulation of memory B cells, most of which lack the classical CD27 marker for memory B cells in humans. The FcRH4⁺ and FcRH4^– memory B cells have undergone comparable levels of immunoglobulin isotype switching and somatic hypermutation, while neither subpopulation expresses the transcription factors involved in plasma cell differentiation. The FcRH4⁺ memory cells are morphologically distinctive large lymphocytes that express the CD69, CD80, and CD86 cell activation markers. They are also shown to be poised to secrete high levels of immunoglobulins in response to stimulation with T cell cytokines, but they fail to proliferate in response either to BCR ligation or Staphylococcus aureus stimulation. A heightened expression of the CCR1 and CCR5 chemokine receptors may facilitate their preferential localization in lymphoid tissues near epithelial surfaces. Cell surface FcRH4 expression thus marks a unique population of memory B cells with distinctive morphology, functional capabilities, and tissue localization.

C.-M. Leu's present address is Department of Medical Research and Education, Veterans General Hospital-Taipei, Taipei City, Taiwan 11217.

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