DIFFERENTIAL-EFFECTS OF RETINOIDS ON POKEWEED MITOGEN INDUCED B-CELL PROLIFERATION VS IMMUNOGLOBULIN-SYNTHESIS

The effects of three retinoids, all-trans-retinoic acid (RA), 13-cis-retinoic acid (cRA), and N-(4-hydroxyphenyl) retinamide (4-HPR) on mouse splenocyte responses to pokeweed mitogen (PWM) and Escherichia coli lipopolysaccharide (LPS) in vitro were evaluated. All three retinoids caused a dose-dependent increase in the proliferative response to PWM. The retinoids hierarchy of efficacy based on potentiation of PWM-induced splenocyte proliferation was RA > cRA > 4-HPR. 13-cis-retinoic acid and 4-HPR also resulted in significant increases in Ig secretion in response to PWM. However, RA did not produce a significant increase in secretion compared with cells treated with PWM alone. The efficacy hierarchy of retinoids ability to potentiate Ig secretion was 4-HPR > cRA > RA. All three compounds did not affect Ig secretion from LPS-stimulated splenocytes and produced dose dependent decreases in proliferation. Both inhibition of LPS-induced proliferation and potentiation of PWM-induced proliferation were maximal when the retinoids were added during the first hour of culture. These results indicate that retinoids have a differential effect on Ig secretion and B-cell proliferation based on structural differences of the retinoids. Potentiation of proliferation and Ig secretion are both T-cell dependent and could be a result of increased lymphokine synthesis by the T-cells or increased responsiveness to the effects of the T-cell produced lymphokines.