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-cell pathway in the spleen.
Schilizzi
B M
BM
Department of Clinical Immunology, University Hospital, Groningen, The Netherlands.
Savelkoul
H F
HF
de Jonge
M W
MW
The
T H
TH
de Leij
L
L
D000818:Animals; D000921:Antibody-Producing Cells / Q000187:drug effects; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D004136:Dinitrobenzenes / Q000276:immunology; D005260:Female; D006825:Hybridomas / Q000187:drug effects; D015847:Interleukin-4 / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000187:drug effects* / Q000473:pathology
D004136:Dinitrobenzenes; D015847:Interleukin-4