IMPAIRED ANTIGEN-SPECIFIC B-CELL RESPONSE AND ALTERED SPLENIC MICROSTRUCTURE IN MICE FOLLOWING CONTINUOUS ADMINISTRATION OF IL-4 IN-VIVO

The effect of long term in vivo administration of IL-4 on the induction of antigen-specific B cells, the splenic microenvironment and the yield of antigen-specific antibody producing hybridomas was studied.Immunization with DNP-KLH, followed by 12 weeks continuous IL-4 treatment resulted in increased numbers of total splenic (non-DNP) IgM and IgG AFC (antibody forming cells) on day 5 after booster, whereas the DNP-specific IgG and IgG1 AFC were reduced compared to age-matched control animals not treated with IL-4. In addition, an almost 300-fold increase in non-DNP IgE was found while the IgE anti-DNP response was minimal.When the splenic cells were used in a fusion protocol, a relative decrease in yield of antigen-specific hybridomas was found in the long term IL-4 treated mice. Immunohistological staining of spleen sections from mice treated with IL-4 up until the time of booster revealed reduced B-cell follicle area and germinal centre numbers. These results show that extensive IL-4 treatment reduced antigen-specific B-cell formation and suggests a reduction in the number of B cells entering the memory B-cel pathway in the spleen.