Discriminating gene expression profi les of memory B cell subpopulations G ö tz

The Rockefeller University Press $30.00 J. Exp. Med. www.jem.org/cgi/doi/10.1084/jem.20072682 Cite by DOI: 10.1084/jem.20072682 1 of 11 Protective immunity elicited by T cell – dependent antigens may last for decades without further exposure to the immunizing antigen ( 1, 2 ), and the memory B (B Mem ) cells serve an important role in sustaining humoral immunity. A defi ning characteristic of B Mem cells is their ability to respond rapidly upon reencounter with their cognate antigens. Most B Mem cells in humans are characterized by their expression of CD27 and switched Ig isotype ( 3 – 5 ). However, recent reports describe an additional population of tissuebased B Mem cells that do not express CD27 ( 6 – 9 ) but instead express Fc receptor – like 4 (FCRL4) ( 7 ). FCRL4 is a member of a recently identifi ed family of transmembrane proteins with immunoregulatory potential, fi ve of which display preferential B cell expression (for review see reference 10 ). Originally identifi ed as a translocation fusion partner in a myeloma cell line, FCRL4 was named immunoreceptor superfamily translocation-associated 1 ( 11 ), and an independent identifi cation through its sequence similarity to known Fc receptors led to the name Fc receptor homologue 4 ( 12 ). A unifi ed nomenclature was recently adopted in which this gene was renamed FCRL4 ( 13 ). FCRL4 expression is restricted to a subpopulation of B Mem cells with a distinctive phenotype and tissue localization pattern ( 7, 14 ). Its intracellular domain contains three consensus immunoreceptor tyrosine-based inhibition motifs, and coligation of FCRL4 with the BCR aborts BCRmediated signaling via recruitment of the Src homology 2 domain – containing phosphatase 1 (SHP-1) and/or SHP-2 tyrosine phosphatases ( 15 ). CORRESPONDENCE Max D. Cooper: [email protected]