Absence of interleukin-4 enhances germinal center reaction in secondary immune response.
The germinal center (GC) is a compartment for B cell differentiation and proliferation. Interleukin (IL)-4 has been considered essential for GC functioning. To define the role of IL-4 in GC reaction, immunohistology of draining lymph nodes (LNs) of IL-4 gene-targeted (IL-4(-/-)) mice was performed during secondary immune response. IL-4(-/-) mice were immunized with ovalbumin emulsified in Freund' complete adjuvant. Final antigen challenge was done 4 weeks later. IL-4(-/-) mice had a higher production of IgG2a and IgG2b and a lower production of IgG1 than those in wild-type (WT) mice. In comparison with WT mice, LNs of IL-4(-/-) mice on days 4 and 7 after final antigen challenge were larger and contained a markedly greater number of GCs, which showed marked size variations with a large number of small GCs and a small number of markedly large GCs. By day 14, the number of GCs decreased to the same level as that in WT mice. However, the LN size in IL-4(-/-) mice was still larger than that in WT mice due to the presence of markedly large GCs. Although well-developed complement receptor(+) follicular dendritic cell (FDC) networks were present in GCs of IL-4(-/-) mice, no FDCs of mature phenotype (CD23(+)) were observed in many of the small GCs. In conclusion, the absence of IL-4 enhanced GC reaction and specific antibody response of Th1-type. IL-4 may play an important role in inducing the appropriate magnitude of humoral immune response.
Andoh
A
A
Department of Pathology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Tokyo, Japan. ando@research.twmu.ac.jp
Masuda
A
A
Yamakawa
M
M
Kumazawa
Y
Y
Kasajima
T
T
D000818:Animals; D020566:Dendritic Cells, Follicular / Q000276:immunology; D018858:Germinal Center / Q000276:immunology*; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology*; D008198:Lymph Nodes / Q000033:anatomy & histology / Q000166:cytology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D011951:Receptors, Complement / Q000276:immunology; D017455:Receptors, IgE / Q000276:immunology
D007074:Immunoglobulin G; D011951:Receptors, Complement; D017455:Receptors, IgE; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin