Interleukin 10, a novel B cell stimulatory factor: unresponsiveness of X chromosome-linked immunodeficiency B cells.

Abstract

SummaryHighly purified, small dense splenic B cells from unstimulated mice showed increased expression ofclass II major histocompatibility complex (MHC) antigens and enhanced viability when cultured with affinity-purified recombinant interleukin 10 (HIA0), compared with B cells cultured in medium alone. These responses were blocked by a monoclonal antibody (mAb) specific for 11,10, but not by an isotype-matched control antibody. IL10 did not upregulate the expression of Fce receptors (CD23) or class I MHC antigens on small dense B cells or induce their replication as monitored by [3H]thymidine incorporation. While these B cell-stimulatory properties of IWO are also mediated by ID4, the two cytokines appear to act independently in these assays ; anti-IL10 antibodies blocked 1140 but not I14-mediated B cell viability enhancement, and vice versa. Similarly, since IIr4 upregulates CD23 on small dense B cells, the inability of IIr10 to do so argues against its acting via endogenously generated 114. Finally, IIA0 did not upregulate class II MHC antigens on B cells from X chromosome-linked immunodeficiency (XID) mice, while the same cells showed normal upregulation of class II antigens in response to 11.4. This report also extends our understanding of the relationship between IIA0 and the highly homologous Epstein-Barr virus (EBV)-encoded Barn HI fragment C rightward reading frame no. 1 (BCRFI) protein. It has previously been shown that BCRFI protein exhibits the cytokine synthesis inhibitory activity of IL10. This report indicates that BCRFI protein also enhances in vitro B cell viability, but does not upregulate class II MHC antigens on B cells. One explanation for these data is that 111,10 contains at least two functional epitopes, only one ofwhich has been conserved by EBV Blymphocytescontribute to the immune response by their production of specific antibodies in response to antigenic stimuli. This process is regulated by a subset of soluble glycoproteins collectively termed cytokines (1-3). The precise number of cytokines involved and their modes of action require further clarification. 11,10 (originally designated cytokine synthesis inhibitory factor [CSIF]l; 4) is a cytokine produced by activated type 2 T helper (Th2) cells (4, 5) and B cells (6, 7), which has the property ofsuppressing cytokine production by type 1 T helper (Thl) cells (4). Isolation of the cDNA for mouse RAO (8) revealed a striking homology between ' Abbreviations used in this paper: BCRFI, BamHI fragment C rightward reading frame no. 1 ; CSIF, cytokine synthesis inhibitory factor; MTT, (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide; SA, streptavidin; Thl/Th2, type 1/type 2 T helper cells; XID, X chromosome-linked immunodeficiency. this cytokine and a previously uncharacterized open reading frame, designated BamHI fragment C rightward reading frame no. 1 (BCRFI), in the EBV genome. Subsequent expression and testing of the protein encoded by BCRFI revealed that this molecule also mediated suppression of Thl cytokine production (...

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