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*
Departments of Pediatrics and Pathology, Women & Infants’ Hospital and
Department of Medicine, Rhode Island Hospital, Brown University, Providence, RI 02905;
Department of Pathology, Roger Williams Medical Center, Providence, RI 02908;
Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912; and
¶ Institut National de la Santé et de la Recherche Médicale Unité 131, Clamart, France
Recent studies have defined several phenotypic and molecular
changes associated with the maturation of naive human B cells within
the milieu of germinal centers. Although naive B cells serve as natural
precursors to germinal center (GC)/memory (M) subpopulations, little is
known about the physiological requirements for the survival of the
naive B cell pool in the absence of cell-cell contact or Ag-mediated
activation. Because IL-4 induces expression of several membrane
receptors such as CD23 which are uniquely present on resting human
naive B lymphocytes, we hypothesized that these cells might be
intrinsically programmed to respond to IL-4 in the absence of cell
division. Using buoyant density-dependent isolation and further
enrichment by negative/positive selection of human naive and GC/M
subpopulations, we characterized cytokine receptor moieties on these
cells and analyzed their survival and growth in the presence of IL-4 or
IL-10. Resting naive B cells expressed significantly higher IL-4
receptor 
-chain on their cell surface than the combined GC/M
subpopulation. The IL-10 receptor and the IL-2 receptor 
c chain were
almost equally expressed on both subpopulations. When cultured in
vitro, the addition of IL-4, but not IL-10, protected naive B cells
from apoptosis in the absence of activation and growth. However, IL-4
exerted no such effect on resting GC/M B cells. These data support the
hypothesis that IL-4 plays a pivotal role in the survival and
maintenance of resting human naive B cells.
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