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The factors regulating growth and patterning of the spleen are poorly defined. We demonstrate here that spleens from B cell-deficient mice have 10-fold reduced expression of the T zone chemokine, CCL21, a threefold reduction in T cell and dendritic cell (DC) numbers, and reduced expression of the T zone stromal marker, gp38. Using cell transfer and receptor blocking approaches, we provide evidence that B cells play a critical role in the early postnatal development of the splenic T zone. This process involves B cell expression of lymphotoxin (LT)alpha1beta2, a cytokine that is required for expression of CCL21 and gp38. Introduction of a B cell specific LTalpha transgene on to the LTalpha-deficient background restored splenic CCL21 and gp38 expression, DC numbers, and T zone size. This work also demonstrates that the role of B cells in T zone development is distinct from the effect of B cells on splenic T cell numbers, which does not require LTalpha1beta2. Therefore, B cells influence spleen T zone development by providing: (a) signals that promote T cell accumulation, and: (b) signals, including LTalpha1beta2, that promote stromal cell development and DC accumulation. Defects in these parameters may contribute to the immune defects associated with B cell deficiency in mice and humans.

Type

Journal article

Journal

J Exp Med

Publication Date

03/12/2001

Volume

194

Pages

1649 - 1660

Keywords

Animals, B-Lymphocytes, Cell Differentiation, Chemokine CCL19, Chemokine CCL21, Chemokine CXCL13, Chemokines, CC, Chemokines, CXC, Dendritic Cells, Gene Expression Regulation, Lymphocyte Count, Lymphotoxin-alpha, Lymphotoxin-beta, Membrane Proteins, Mice, Mice, Inbred C57BL, Mice, Knockout, Spleen, Stromal Cells, T-Lymphocytes