Estrogen deficiency stimulates B lymphopoiesis in mouse bone marrow.

Abstract

We have found that an estrogen deficiency causes a marked increase in bone marrow cells. To examine the effect of estrogen on hemopoiesis, we characterized the increased population of bone marrow cells after ovariectomy (OVX). In OVX mice, the percentage of myeloid cells and granulocytes was decreased, whereas that of B220-positive B lymphocytes was selectively increased 2-4 wk after surgery. The total number of myeloid cells and granulocytes did not change appreciably, but that of B220-positive cells was greatly increased by OVX. When OVX mice were treated with estrogen, the increased B lymphopoiesis returned to normal. B220-positive cells were classified into two subpopulations, B220I0W and B220i9'h. The majority of the B220'W cells were negative for the IgM ,u chain, whereas most of the B220"'4" cells were ,i-positive. OVX selectively increased the precursors of B lymphocytes identified by B2201w. ,unegative phenotype, suggesting that an estrogen deficiency stimulates accumulation of B lymphocyte precursors. When bone marrow-derived stromal cells (ST2) were pretreated with estrogen then co-cultured with bone marrow cells in the presence of estrogen, the stromal cell-dependent B lymphopoiesis was greatly inhibited. The present study suggests that estrogen plays an important role in the regulation of B lymphocyte development in mouse bone marrow. (J. Clin.

RANKL (Receptor Activator of NFκB Ligand) Produced by Osteocytes Is Required for the Increase in B Cells and Bone Loss Caused by Estrogen Deficiency in Mice

“…2, B-D). The effect on monocytes has been observed previously and is likely a consequence of the increase in the percentage of B cells (11). Supporting this idea, the total number of B cells isolated by magnetic bead separation was elevated in ovariectomized Tnfsf11 f/f but not Tnfsf11 ⌬Ot mice (Fig.…”

“…An increase in B cell number is one of the most consistently observed changes in the bone marrow of estrogen-deficient mice (10,11,39). Because this increase is coincident with bone loss and because of the juxtaposition of the bone marrow with bone matrix, Suda and co-workers (40) proposed a causal link between the increase in B cell number and the elevated bone resorption caused by estrogen deficiency.…”

“…Estrogen deficiency also causes a striking increase in B lymphocyte number in the bone marrow (10,11). Moreover, deletion of the Tnfsf11 gene from B cells prevents both the increase in B cell number and the increase in cancellous osteoclast number caused by ovariectomy (12).…”

Estrogen and Angiogenesis

“…An effect of estrogen on hematopoietic stem cells and granuloid progenitors has been noted for Ͼ2 decades. [57][58][59][60] Estrogen deficiency has been shown to stimulate ␤-lymphopoiesis in bone marrow 61 and to increase osteoblastogenesis. 62 Peripheral blood monocytes as well as T and B cells have been shown to express intact estrogen receptor-␣, 63 and an intact estrogen receptor transactivation domain has been shown to be required for estradiol to inhibit the differentiation of avian erythroid progenitors.…”

Role of B Lymphocytes in New Bone Formation

“…Estrogen, a powerful regulator of bone mass, is involved in the differentiation of the B-cell hematopoietic lineage (Smitson et al, 1995) and increased B-lymphopoiesis may be involved in the mechanism of stimulated bone resorption that is seen with estrogen deficiency (Masuzawa et al, 1994). Mice with a gene knockout for nuclear transcription factor ⑂B (NF-⑂B), whose activation is involved in the survival of osteoclasts (Jimi et al, 1998), fail to generate both B lymphocytes and mature osteoclasts (Franzoso et al, 1997).…”