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.

Threshold levels of Flt3‐ligand are required for the generation and survival of lymphoid progenitors and B‐cell precursors

“…For example, haploinsufficiency of B‐cell‐activating‐factor decreased serum immunoglobulin levels, consistent with a critical role for B‐cell‐activating‐factor in B‐cell homeostasis 29. Similarly, reductions in IL‐7 responding cells in BM of pregnant mice were restored by exogenous administration of IL‐7 30. Exogenous administration of FL has been shown to increase numbers of LSK + Flt3 + and B220 + ckit lo Flt3 + BCP in BM in vivo 14, 15.…”

Pregnancy alters the circulating B cell compartment in atopic asthmatic women, and transitional B cells are positively associated with the development of allergy manifestations in their progeny

“…Estradiol, a pregnancy‐associated hormone that peaks in the third trimester, has also been considered relevant for B cell modulation, through its negative effect on IL‐7 . Decreased IL‐7 availability during pregnancy arrests B lymphopoiesis . At the same time, progesterone, another hormone peaking in the last weeks of gestation, directly inhibits B cell activation in mice, which can also explain the accumulation of mature, non‐activated B cells during pregnancy.…”

Soluble Frizzled-Related Protein 1 Is Estrogen Inducible in Bone Marrow Stromal Cells and Suppresses the Earliest Events in Lymphopoiesis

“…For example, estrogen might directly cause sFRP production in some hematopoietic cells. Rolink and colleagues recently found two-fold reductions in bone marrow IL-7 mRNA during pregnancy (56). Residual IL-7 responding progenitor in pregnant mouse marrow expanded when exposed to high concentrations of this essential cytokine.…”