Suppression of B lymphopoiesis during normal pregnancy.

Abstract

SummaryWe describe a dramatic reduction in numbers and activity of committed B lymphocyte precursors in the bone marrow of normal pregnant mice. Changes in cells responsive to were evident as early as 6.5 d of pregnancy and values were <10% of normal at parturition. B lineage precursors, identified by display of CD45R and absence of surface IgM, were also substantially depressed, and subpopulations representing different stages in the B lineage were assessed by three-color flow cytometry. Early pro-B ceUs are medium to large in size and have been previously characterized by low expression of the heat-stable antigen (HSA). This category of cells was not reduced, and in fact may have been slightly elevated, during pregnancy. In contrast, all subsequent populations of B lineage precursors, defined by patterns of expression of heat-stable and CD43 antigens, were substantially depressed. The immediate precursors of B cells (small pre-B cells) were identified by small size, expression of CD45R, absence of CD43, and lack of surface IgM. These were the most reduced of any phenotypically defined population in bone marrow. Numbers of newly formed B ceUs, characterized by the presence of sIgM, but not slgD, were also diminished. However, B cells with a mature phenotype (slgM + , slgD +) were present in normal to somewhat devated numbers. Mitogen-responsive B cells donable in a semisolid agar assay were not significantly affected. A bromodeoxyuridine (BrdU) labeling technique was used to evaluate mitotic activity, which revealed an increased proportion of long-lived lymphocytes in the bone marrow of pregnant mice_ These observations indicate that B lymphopoiesis is markedly downregulated during pregnancy and that all precursor populations beyond the early pro-B cell stage are affected. The pregnancyrelated changes in bone marrow were selective for B lineage precursors, as cells expressing myeloid and erythroid markers were not reduced. In spleen, evidence was obtained for partial depletion of one subset of B cells. These cells, which have been reported to be recent immigrants from marrow, are characterized as having high levels of sIgM and HSA. Changes in other major B lymphocyte subsets in the spleen were less remarkable. When considered with results from the BrdU labeling procedure, the findings indicate that both production and export of lymphocytes from marrow may be substantially decreased. Numbers of B cell precursors were higher in postpartum animals whose litters wereremoved at birth, suggesting that lactation may prolong regeneration of lymphocyte production. We also found that acute estrogen treatment selectively reduced numbers of B lymphocyte precursors in bone marrow. These observations raise the interesting possibility that endocrine mechanisms involving sex steroids may be important for normal regulation of B lymphopoiesis.

Progesterone and estradiol exert an inhibitory effect on the production of anti-inflammatory cytokine IL-10 by activated MZ B cells

“…Previously, we have shown that pre-activated MZ B cells numbers were increased in the spleen during pregnancy and proposed that this may represent an evolutionary acquired mechanism tending to overcome the strong reduction of B cell lymphopoiesis occurring during this critical period of time, thus ensuring a proper defense (Medina et al, 1993;Muzzio et al, 2014). Indeed, using a mouse model of pregnancy failures (Bobé et al, 1986) we could later confirm the crucial role of MZ B cells in pregnancy wellbeing by showing that pregnant mice developing normal pregnancies but not those suffering from pregnancy failures display an expansion of the MZ B cell compartment (Muzzio et al, 2016).…”

Adiponectin, a Fat Cell Product, Influences the Earliest Lymphocyte Precursors in Bone Marrow Cultures by Activation of the Cyclooxygenase-Prostaglandin Pathway in Stromal Cells

“…Bone marrow or spleen cells were prepared and suspended in 1 ml of assay medium as described (32). The semisolid agar colony-forming units (CFU) assay for lymphoid clones responsive to IL-7 used 1 ng/ml recombinant mouse IL-7.…”

Leptin increases maternal investment

“…It would therefore make sense that this energetically costly process is suppressed in pregnant leptin-treated females in response to increased reproductive investment. Most studies across mammalian species demonstrate decreased immunity, including production of certain antibodies, during pregnancy (Weinberg 1984;Medina et al 1993). In fact, previous studies in Siberian hamsters show decreased anti-KLH IgM response during pregnancy (Drazen et al 2003).…”