Splenic T Zone Development Is B Cell Dependent
Ngo VN., Cornall RJ., Cyster JG.
<jats:p>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)α1β2, a cytokine that is required for expression of CCL21 and gp38. Introduction of a B cell specific LTα transgene on to the LTα-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 LTα1β2. Therefore, B cells influence spleen T zone development by providing: (a) signals that promote T cell accumulation, and: (b) signals, including LTα1β2, 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.</jats:p>