Activated B cells express receptors for, and proliferate in response to, pure interleukin 2.

Abstract

Interleukin 2 (IL-2) 1 was discovered through its function as a T cell growth factor (TCGF) (1, 2). Indeed, the availability of T cell lines for the quantitative measurement of TCGF activity has been crucial for the characterization of IL-2 (3, 4) and IL-2 receptors on activated T cells (5-7) in different species. Human IL-2, which acts on murine and human T cells (4,8,9), can now rapidly be purified to apparent homogeneity with monoclonal antibodies (8, 9) and its cDNA has been cloned (10, 11). Human I L-2 is a T ceil-generated 15 kilodalton peptide hormone of 133 amino acids.Although it was observed in several studies (3, 4, 12-14) that IL-2-rich T cell supernatants (SN) enhance the generation of plaque-forming cells (PFC) in certain B cell culture systems, it is widely believed that B cells do not directly respond to IL-2. Thus, a variety of other T cell-derived factors (but not IL-2) were reported to enhance the proliferation of B cells activated by either Tindependent antigens (15), dextran (16), lipopolysaccharide (LPS) (17, 18), antiimmunoglobulin antibodies (anti-Ig) (16,(19)(20)(21), or other means (22). In one study (23), showing an effect of immunoaffinity-purified IL-2 on anti-Iginduced B cell proliferation, the interpretation of the results was complicated because it was also observed that T cells participated in the B cell response. LPSactivated murine B cells were not found to bind radiolabeled IL-2 (5) but, in another study (7), such LPS blasts reacted weakly with an anti-IL-2 receptor monoclonal antibody.However, there still exist controversies with regard to the activation signals that B cells require to respond to growth factors (24). A recent study (25) showed in a limit-dilution culture system for murine B cells that, in fact, either a cell contact-dependent T-B cell interaction or LPS was required in conjunction with anti-Ig for optimal induction of growth factor responsiveness. Whereas anti-Ig

Human High Molecular Weight Melanoma-Associated Antigen Mimicry by Mouse Anti-Idiotypic Monoclonal Antibody MK2-23: Enhancement of Immunogenicity of Anti-Idiotypic Monoclonal Antibody MK2-23 by Fusion with Interleukin 2

“…The central role of IL-2 as an adjuvant is based primarily on its ability to trigger the proliferation and differentiation of antigen-specific lymphocytes, particularly CD4 + T helper cells (39) but also including B cells (39,40) and CD8 + T cells (41). Our findings parallel those of other investigators who have used anti-idiotypic antibodies conjugated to immunostimulatory cytokines as immunogens.…”

Interleukin-2: Biology, Design and Application

“…Furthermore, activated mouse and human B cells express functional trimeric IL-2Rs and proliferate in vitro on stimulation with human IL-2 (hIL-2) [32,33]. Interestingly, DCs have been reported to express CD25 and to use CD25 to present IL-2 in trans to T cells expressing dimeric IL-2Rs [23,34] (Figure 2).…”

Safety assessment of immunomodulatory biologics: The promise and challenges of regulatory T-cell modulation

“…The identification and availability of this cytokine as an experimental tool enabled in vitro experimentation on cloned T-cells with single antigenic specificity to probe the nature of the receptors, cytokines, and signaling pathways involved in T-cell activation and cell fate determination (Oppenheim, 2007). Subsequent work also revealed pleiotropic activity of IL-2 in activating NK cells (Henney et al, 1981) and B-cells (Zubler et al, 1984) in addition to T-cells. This work, which was largely conducted in vitro, resulted in a prevailing model wherein activation of the T-cell, with co-stimulation via CD28 and other molecules, results in IL-2 production and increased expression of IL-2 receptor (IL-2R), which subsequently drive extensive clonal expansion and development of effector function (Malek, 2008).…”