THE EFFECTS OF RETINOIC ACID ON INVITRO IMMUNOGLOBULIN-SYNTHESIS BY CORD BLOOD AND ADULT PERIPHERAL-BLOOD MONONUCLEAR-CELLS

Retinoic acid (RA) has attracted considerable attention as an agent with a broad range of physiologic and metabolic effects. The importance of RA in the susceptibility of vitamin A-deficient animals and humans to infection is well known. Initial studies from our laboratory showed that RA augmented the IgM response of cord blood mononuclear cells (CBMC) at concentrations ranging from 10-5 to 10-8M, but not adult peripheral blood mononuclear cells (PBMC), to formalinized Cowan I strain Staphylococcus aureus (SAC), a T-cell-dependent polyclonal B-cell activator. In the present study, we demonstrate that RA augments the SAC-stimulated IgG synthesis of adult PBMC at very low concentrations (10-11 to 10-13M ) indicating that adult PBMC is 104 to 106 times more responsive to the augmenting effects of RA than CBMC. To evaluate the differences in dose-response characteristics between CBMC and adult PBMC, co-mixture experiments between T- and B-cells of CBMC and adult PBMC were performed. The dose-response characteristics of the augmenting effects of RA for a particular Ig isotype were related to the responding B-cell population. The results of an ELISA spot assay showed that the RA-induced enhancement in Ig synthesis was due to the "recruitment" of more B-cells to differentiate into Ig-secreting cells. When RA was added to CBMC stimulated by EBV, a T-cell-independent polyclonal activator, or to EBV-transformed B-cell clones, a small (twofold) augmentation in IgM synthesis was seen which suggested that RA may also have some direct effect on B-cells. However, if cord blood T-cells were preincubated with RA for 36 hr, washed, and added to cord blood B-cells with SAC, a 2.5- to 9-fold augmentation in IgM was obtained, These studies suggest that the principal mechanism(s) by which RA augments the Ig synthesis of SAC-stimulated cultures is mediated by the T-cell, or T-cell products, e.g., cytokines, which induces an increased proportion of B-cells to differentiate into Ig-secreting cells. RA may also have an effect, although minor, directly on B-cells. The differences in the dose-response characteristics between CBMC and adult PBMC appears to reside within the intrinsic capabilities of an Ig-producing B-cell subpopulation. © 1993 Academic Press. All rights reserved.