title: 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 CD21(high)CD23(low) 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.
authors.affiliation: Laboratory of Experimental Transplantation, University of Leuven, Leuven 3000, Belgium.
authors.forename: Leen
authors.initials: L
authors.lastname: Willems
authors.forename: Shengqiao
authors.initials: S
authors.lastname: Li
authors.forename: Omer
authors.initials: O
authors.lastname: Rutgeerts
authors.forename: Caroline
authors.initials: C
authors.lastname: Lenaerts
authors.forename: Mark
authors.initials: M
authors.lastname: Waer
authors.forename: An D
authors.initials: AD
authors.lastname: Billiau
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D002469:Cell Separation; D006224:Cricetinae; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D016027:Heart Transplantation; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000276:immunology; D015851:Interleukin-7 / Q000276:immunology* / Q000378:metabolism; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013154:Spleen / Q000166:cytology* / Q000276:immunology; D014183:Transplantation, Heterologous
chemical_list: D007075:Immunoglobulin M; D015851:Interleukin-7