Absence of interleukin-4 enhances germinal center reaction in secondary immune response

Immunol Lett. 2000 Jul 3;73(1):35-41. doi: 10.1016/s0165-2478(00)00202-9.


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.

MeSH terms

  • Animals
  • Dendritic Cells, Follicular / immunology
  • Germinal Center / immunology*
  • Immunization, Secondary
  • Immunoglobulin G / blood
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology
  • Interleukin-4 / genetics
  • Interleukin-4 / immunology*
  • Lymph Nodes / anatomy & histology
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Ovalbumin / immunology
  • Receptors, Complement / immunology
  • Receptors, IgE / immunology


  • Immunoglobulin G
  • Receptors, Complement
  • Receptors, IgE
  • Interleukin-4
  • Interferon-gamma
  • Ovalbumin