IL-7 Is Required for the Development of the Intrinsic Function of Marginal Zone B Cells and the Marginal Zone Microenvironment

Abstract

The characteristic microarchitecture of the marginal zone (MZ), formed by locally interacting MZ-specific B cells, macrophages, and endothelial cells, is critical for productive marginal zone B cell (MZB cell) Ab responses. Reportedly, IL-7–deficient mice, although severely lymphopenic, retain small numbers of CD21highCD23low B cells consistent with MZB cell phenotype, suggesting that IL-7 signaling is not exclusively required for MZB cell lymphopoiesis. In this study, we investigated the function of IL-7−/− MZB cells and the IL-7−/− microenvironment using a model of hamster heart xenograft rejection, which depends exclusively on MZB cell-mediated production of T cell-independent IgM xenoantibodies (IgMXAb). C57BL/6-IL-7−/− mice accepted xenografts indefinitely and failed to produce IgMXAb, even after transfer of additional IL-7−/− or wild-type C57BL/6 MZB cells. Transfer of wild-type but not IL-7−/− B cells enabled SCID mice to produce IgMXAb. When transferred to SCID mice, wild-type but not IL-7−/− B cells formed B cell follicles with clearly defined IgM+, MOMA-1+, and MAdCAM-1+ MZ structures. Conversely, adoptively transferred GFP+ C57BL/6 B cells homed to the MZ area in a SCID but not an IL-7−/− environment. Naive IL-7−/− mice showed absent or aberrant splenic B cell structures. We provide evidence that IL-7 is critical for the development of the intrinsic function of MZB cells in producing rapidly induced IgM against T cell-independent type II Ags, for their homing potential, and for the development of a functional MZ microanatomy capable of attracting and lodging MZB cells.