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

Deregulated overexpression of IL-7 under the control of the promoter of the E alpha gene of MHC class II in IL-7-transgenic mice changes B cell develo pment in wild-type mice and in mutants which limit B cell development at va rious cellular stages. While the introduction of deregulated IL-7 productio n does not change the size of the pro-B and pre-B I compartments in the bon e marrow of wild-type and lambda(5)(-/-) mice, it increases these compartme nts 2.5- to fivefold in mice which cannot make immature and mature B cells, i.e. in RAG-2(-/-), tm mu H-/-, and RAG-2(-/-) mice expressing a transgeni c mu H chain. Excessive IL-7 production also increases four- to fivefold th e pre-B II compartment in all those mouse strains where it can be formed (i .e. in wild-type, lambda 5(-/-) and mu H chain-transgenic RAG-2(-/-) mice), while no pre-B-II-like cells appear in excessively IL-7-stimulated bone ma rrow of mice devoid of pre-B II cells (i.e. in tm mu H-/- and RAG-2(-/-) mi ce). 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 an d 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 l imits cellular expansion and provokes spillover into the peripheral lymphoi d organs.