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International Immunology, Vol. 11, No. 4, 509-518, April 1999
© 1999 Japanese Society for Immunology

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

Maria Isabel D. Rossi1, Hélio S. Dutra2, Márcia C. El-Cheikh3, Adriana Bonomo4 and Radovan Borojevic2,3

1 Departamento de Patologia, Hospital Universitário António Pedro, Universidade Federal Fluminense, Niterói, Brazil
2 Programa Avanciado de Biologia Celular Aplicada à Medicina, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Brazil
3 Departamento de Histologia e Embriologia, Instituto de Ciências Biomédicas, and
4 Departamento de Imunologia, Instituto de Microbiologia, Universidade Federal do Rio de Janeiro, Brazil

Correspondence to: R. Borojevic, Caixa Postal 68021, 21941-970 Rio de Janeiro, Brazil

Inflammatory granulomatous reactions in liver elicited by schistosomal infection have been shown to function as active extramedullar myelopoietic sites, producing potentially all the myeloid lineages. We have now addressed the question of the extramedullar B lymphopoiesis in these sites. We have shown 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-B cells in the bone marrow of one femur. In agreement with their phenotype, the RT-PCR analysis showed that these cells expressed RAG-1 and {lambda}5 genes. However, the conversion of the pro-B to pre-B cells was not observed and no clonogenic B cell precursors could be detected in semi-solid cultures stimulated by IL-7. The granulomatous stroma was shown to produce IL-7 and express c-kit, and was able to sustain the full B lymphopoiesis in vitro. Conversely, the granuloma supernatant was shown to inhibit actively the development of B lymphocytes. We conclude that the granuloma environment elicits homing and proliferation of totipotent hematopoietic precursors, and that it is permissive for early commitment to the B cell lineage, but the full extramedullar production of B cell is abrogated by soluble factors produced inside the granulomas.

Keywords: B220, B cell precursors, B lymphocytes, c-kit, CD43, IL-7, inflammation, hematopoietic stroma, {lambda}5, RAG-1, schistosomiasis

Transmitting editor: R.L. Coffman


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