RETINOIDS AS IG ISOTYPE-SWITCH MODULATORS - THE ROLE OF RETINOIDS IN DIRECTING ISOTYPE SWITCHING TO IGA AND IGG1 (IGE) IN ASSOCIATION WITH IL-4 AND IL-5

The role of retinoids was analyzed in directing isotype switching to I gA and IgG1 (IgE) by LPS-stimulated murine mu(+)B-cells in the presenc e of two Th2-type cytokines, IL-4 and IL-5. All brans retinoic acid (R A) enhanced the production of IgA at high concentrations (10-100 nM) i n the presence of IL-5. Addition of IL-4 to the system modulated the I gA response in a dose-dependent manner. Namely, IL-4 inhibited the res ponse at concentrations higher than 250 u/ml, but showed slight enhanc ement at lower concentrations (130 u/ml). IL-4 alone, which is conside red to be an IgE isotype-switch inducer, strongly enhanced the IgG1 an d IgE responses. Addition of IL-5 to the system showed a synergistic e ffect which could be attenuated by addition of low concentrations of R A (about 1 nM). Thus, the presence of switch modulators such as IL-4 a nd IL-5, their concentration ratios, and concentrations of retinoids a re crucial factors in initiating and directing isotype switching to Ig A and IgG1 (IgE). (C) 1996 Academic Press, Inc.