Suppression of B lymphopoeisis during normal pregnancy

Kay L Medina, G. Smithson, P. W. Kincade

Research output: Contribution to journalArticle

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Abstract

We 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 IL-7 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 cells 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 cells, characterized by the presence of sIgM, but not sIgD, were also diminished. However, B cells with a mature phenotype (sIgM+, sIgD+) were present in normal to somewhat elevated numbers. Mitogen-responsive B cells clonable 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 pregnancy-related 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 were removed 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.

Original languageEnglish (US)
Pages (from-to)1507-1515
Number of pages9
JournalJournal of Experimental Medicine
Volume178
Issue number5
DOIs
StatePublished - 1993
Externally publishedYes

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B-Lymphoid Precursor Cells
Bone Marrow
Pregnancy
Lymphopoiesis
B-Lymphocyte Subsets
B-Lymphocytes
Hot Temperature
Lymphocytes
Bromodeoxyuridine
Immunoglobulin M
CD43 Antigens
Spleen
Parturition
Population
Antigens
Interleukin-7
Erythroid Cells
Myeloid Cells
Mitogens
Lactation

ASJC Scopus subject areas

  • Immunology

Cite this

Suppression of B lymphopoeisis during normal pregnancy. / Medina, Kay L; Smithson, G.; Kincade, P. W.

In: Journal of Experimental Medicine, Vol. 178, No. 5, 1993, p. 1507-1515.

Research output: Contribution to journalArticle

Medina, Kay L ; Smithson, G. ; Kincade, P. W. / Suppression of B lymphopoeisis during normal pregnancy. In: Journal of Experimental Medicine. 1993 ; Vol. 178, No. 5. pp. 1507-1515.
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