Effect of deregulated IL-7 transgene expression on B lymphocyte development in mice expressing mutated pre-B cell receptors.

Abstract

Deregulated overexpression of IL-7 under the control of the promoter of the Ealpha gene of MHC class II in IL-7-transgenic mice changes B cell development in wild-type mice and in mutants which limit B cell development at various cellular stages. While the introduction of deregulated IL-7 production does not change the size of the pro-B and pre-B I compartments in the bone marrow of wild-type and lambda5-/- mice, it increases these compartments 2.5- to fivefold in mice which cannot make immature and mature B cells, i. e. in RAG-2-/-, tmmuH-/-, and RAG-2-/- mice expressing a transgenic muH chain. Excessive IL-7 production also increases four- to fivefold the pre-B II compartment in all those mouse strains where it can be formed (i. e. in wild-type, lambda5-/- and muH chain-transgenic RAG-2-/- mice), while no pre-B- II-like cells appear in excessively IL-7-stimulated bone marrow of mice devoid of pre-B II cells (i. e. in tmmuH-/- and RAG-2-/- mice). In the spleen of all IL-7-transgenic mice significant numbers of both pro-B and pre-B I cells are detectable and increased numbers of pre-B II and immature B cells appear in the spleen of mouse strains which are capable of making them. The capacity of the spleen to accommodate expanded numbers of these B-lineage cells as well as mature B cells is much larger than that of the bone marrow of the IL-7-transgenic mice probably because the bone limits cellular expansion and provokes spillover into the peripheral lymphoid organs.