Transient decrease in interleukin-7 availability arrests B lymphopoiesis during pregnancy

Abstract

In mice, B lymphopoiesis is transiently arrested during pregnancy, and this is thought to be due to depletion of a hormone-sensitive bone marrow precursor. In this study, combining in vitro and in vivo approaches with detailed phenotypic and functional analysis of progenitor cells, we have investigated the effects of pregnancy on mouse B cell development. Recently, we characterized a BM progenitor called early progenitor with lymphoid and myeloid potential (EPLM) which, when cultured under B cell conditions, is the immediate precursor of pre-B1 cells. Results obtained show that during late pregnancy, B cell development was blocked at the EPLM-to-pre-B1 transition. This block was associated with a lack of IL-7 due to a down-regulation of IL-7 gene transcription. Moreover, we established that exogenously administered IL-7 could rescue B lymphopoiesis in pregnant mice. We conclude that during pregnancy, rather than directly depleting a hormone-sensitive B cell precursor, hormones dampen BM B cell development by fine-tuning IL-7 availability.