Extramedullar B lymphopoiesis in liver schistosomal granulomas: presence of the early stages and inhibition of the full B cell differentiation

Inflammatory granulomatous reactions in liver elicited by schistosomal infe ction have been shown to function as active extramedullar myelopoietic site s, producing potentially all the myeloid lineages. We have now addressed th e question of the extramedullar a lymphopoiesis in these sites. We have sho wn the presence of early B cell precursors (pro-B cells) in the granulomas by immunophenotyping. Their total number in the liver was equivalent to the pro-a cells in the bone marrow of one femur. In agreement with their pheno type, the RT-PCR analysis showed that these cells expressed RAG-1 and lambd a 5 genes. However, the conversion of the pro-a to pre-a cells was not obse rved and no clonogenic B cell precursors could be detected in semi-solid cu ltures stimulated by IL-7, The granulomatous stroma was shown to produce IL -7 and express c-kit, and was able to sustain the full a lymphopoiesis in v itro. Conversely, the granuloma supernatant was shown to inhibit actively t he development of a lymphocytes. We conclude that the granuloma environment elicits homing and proliferation of totipotent hematopoietic precursors, a nd that it is permissive for early commitment to the a cell lineage, but th e full extramedullar production of a cell is abrogated by soluble factors p roduced inside the granulomas.