Transferrin receptor induction is required for human B‐lymphocyte activation but not for immunoglobulin secretion

Abstract

Transferrin receptors are expressed on proliferating cells and are required for their growth. Transferrin receptors can be detected after, but not before, mitogenic stimulation of normal peripheral blood T and B cells. In the experiments reported here we have examined the regulation of transferrin receptor expression on activated human B cells and whether or not these receptors are necessary for activation to occur. Activation was assessed by studying both proliferation and immunoglobulin secretion. We have determined that transferrin receptor expression on B cells is regulated by a factor contained in supernatants of mitogen-stimulated T cells (probably B-cell growth factor). This expression is required for proliferation to occur, since antibody to transferrin receptor (42/6) blocks B-cell proliferation. Induction of immunoglobulin secretion, however, although dependent on PHA-treated T-cell supernatant, is not dependent on transferrin receptor expression and can occur in mitogen-stimulated cells whose proliferation has been blocked by antitransferrin receptor antibody. In addition, we have demonstrated that IgM messenger RNA induction following mitogen stimulation is unaffected by antitransferrin receptor antibody. These findings support a model for B-cell activation in which mitogen (or antigen) delivers two concurrent but distinct signals to B cells: one, dependent on B-cell growth factor and transferrin receptor expression, for proliferation, and a second, dependent on T cell-derived factors and not requiring transferrin receptors, which leads to immunoglobulin secretion.

Down-regulation of CXCR4 and CD62L in Chronic Lymphocytic Leukemia Cells Is Triggered by B-Cell Receptor Ligation and Associated with Progressive Disease

“…The strong down-regulation of CXCR4 was also associated with a concomitant but to a lesser extent, down-regulation of CD19 on the same subset of cells. As expected, the subset of cells down-regulating both CXCR4 and CD19 up-regulated both CD71 and CD23 expression (data not shown) due to the activation process resulting from BCR engagement (27,28) Supplementary Fig. S1).…”

“…BCR-induced CD62L down-regulation was also variable among cases (Fig. 2C), and similarly to CXCR4, two groups of response were identified, i.e., a group of six cases (UPN 2-7-13-15- [21][22][23][24][25][26][27][28][29] showing no modulation of CD62L expression upon BCR stimulation (CD62L decrease, <5%; negative response), whereas the remaining cases (22 of 28) down-regulated CD62L upon BCR engagement (CD62L decrease, >5%; positive response) but to a variable extent. As observed for CXCR4, two profiles of BCR-induced response were indeed observed among the positive responses (Fig.…”

Transferrin receptor 1 is differentially required in lymphocyte development

“…[29][30][31][32][33][34][35][36] Accordingly, anti-TfR antibodies have been shown to inhibit proliferation of stimulated peripheral lymphocytes. 32,37,38 In mature T cells, TfR expression is induced in response to autocrine activity of interleukin-2 and modulated by cellular iron content. 31,[39][40][41] To further investigate the ability of TfR Ϫ/Ϫ cells to undergo normal lymphocyte differentiation, we took advantage of the sensitive RAG2 Ϫ/Ϫ complementation assay.…”

Regulation of Transferrin Receptor Expression and Control of Cell Growth

“…Following addition of mitogen to purified human B cells, the number of cells positive for surface transferrin receptors increases with time, cor relating with the level of DNA synthesis. Blockade of transferrin receptors on these cells inhibits DNA synthe sis [4],…”