Identification of CD36 as the first gene dependent on the B-cell differentiation factor Oct-2.

Abstract

The Oct-2 transcription factor is expressed predominantly in B lymphocytes and has been shown previously to be important for the terminal phase of B-cell differentiation in mice. A number of genes specifically expressed in B cells contain Oct-2-binding sites in their regulatory regions. However, the analysis of expression levels of these genes in Oct-2-deficient B cells revealed that they were unaffected. Hence, there were no genes known that critically depend on Oct-2 for their expression. To understand the molecular basis for the Oct-2 effect on B-cell development, we searched for Oct-2 target genes by subtractive cDNA cloning. We show here that expression of the murine CD36 gene in B cells and macrophages requires a functional Oct-2 protein. Nuclear run-on experiments demonstrate that this gene is regulated transcriptionally by Oct-2. Moreover, CD36 levels correlated with the levels of Oct-2 expression in several mouse B-cell and macrophage cell lines. Finally, compared to wild-type and heterozygous mice, CD36 mRNA levels were markedly reduced in spleens and B-cell-enriched splenocyte fractions from oct-2 -/-mice. The data identify CD36 as the first target gene critically dependent on Oct-2 for its expression. Because CD36 expression is also dependent on Oct-2 in vivo, it is a candidate gene through which Oct-2 could affect B-cell differentiation.

CD36 Is Differentially Expressed on B Cell Subsets during Development and in Responses to Antigen

“…In addition to the minor populations of FO B cells that express CD36, it was also expressed at a slightly lower level on most MZ precursors and a subset of transitional B cells, suggesting that these cells may be activated. CD36 expression along with other MZ B cell markers such as CD9 and FcRL5 may be indicative of activation signals involved in the (41) showed that CD36 expression is strictly regulated by Oct2 in B cells. Thus, it will also be of interest to check Oct2 expression by B cell subsets.…”

Down-regulation of BOB.1/OBF.1 and Oct2 in classical Hodgkin disease but not in lymphocyte predominant Hodgkin disease correlates with immunoglobulin transcription

“…16,17 Western blot analysis was carried out according to previously published protocols. 16,18 Cell culture and transfection For electroporation, 5 ϫ 10 6 cultured cells were pelleted and resuspended in a final volume of 300 L RPMI medium supplemented with 10% FCS. Fifteen micrograms of the respective luciferase reporter plasmid (details about the wild-type immunoglobulin octamer enhancer and the synthetic multimerized octamer reporter constructs can be found in Laumen et al 12 and Pfisterer et al 19,20 ) were added to the cells.…”

Differential Regulation of the Two Neuronal Nitric-oxide Synthase Gene Promoters by the Oct-2 Transcription Factor

“…In agreement with this idea the immunoglobulin enhancer exhibits a dramatically reduced activity in B cells lacking Oct-2 (6), and knockout mice lacking a functional Oct-2 gene show defects in B cell maturation and response to antigen (7). Moreover, these knockout mice also exhibit a lack of CD36 expression in their B lymphocytes, identifying the gene encoding this factor as another target for activation by Oct-2 in B lymphocytes (8).…”