IL-5-Deficient Mice Have a Developmental Defect in CD5+ B-1 Cells and Lack Eosinophilia but Have Normal Antibody and Cytotoxic T Cell Responses

Abstract

Mice deficient in interleukin-5 (IL-5-/- mice) were generated by gene targeting in embryonal stem cells. Contrary to previous studies, no obligatory role for IL-5 was demonstrated in the regulation of conventional B (B-2) cells, in normal T cell-dependent antibody responses or in cytotoxic T cell development. However, CD5+ B cells (B-1 cells) in the peritoneal cavity were reduced by 50%-80% in 2-week-old IL-5-/- mice, returning to normal by 6-8 weeks of age. The IL-5-/- mice did not develop blood and tissue eosinophilia when infected with the helminth Mesocestoides corti, but basal levels of eosinophils with normal morphology were produced in the absence of IL-5. IL-5 deficiency did not affect the worm burden of infected mice, indicating that increased eosinophils do not play a significant role in the host defence in this parasite model.

IL-5 links adaptive and natural immunity specific for epitopes of oxidized LDL and protects from atherosclerosis

“…Female C57BL/6 mice, MHCII -/-and T cell receptor β -/-mice were from The Jackson Laboratories (Bar Harbor, Maine, USA), and IL-5 -/-mice were a kind gift of Manfred Kopf (ETH Zürich, Zürich, Switzerland) (32). All mice were on a C57BL/6 background and were bred and maintained in our colony.…”

“…Although the secretion of B-1 cell-dependent IgM antibodies is known to be T cell independent, T cells are thought to provide noncognate help for B-1 cells (30), and IL-5 has been described as an important factor in B-1 cell biology (31,32).…”

Eosinophilia is attenuated in experimental colitis induced in IL-5 deficient mice

“…4 Homozygous animals were obtained by breeding of heterozygous parents and were identified by polymerase chain reaction analysis. Mice were fed sterile food and water ad libitum and were regularly checked for viruses and parasites.…”

“…2 Although earlier studies suggested additional activities of IL-5 in regulating mouse B cells and antibody production 3 recent studies with an IL-5 deficient mouse strain indicate that the regulation of eosinophilia may be the only obligatory role for IL-5 in the adult mouse. 4 IL-5 deficient mice, produced by gene targeting of embryonal stem cells, 4 appear to be normal in appearance and do not develop any obvious disease. Tissue eosinophilia induced by parasitic infections is abolished in these mice although baseline numbers of eosinophils are close to normal.…”

Th1 and Th2 CD4+ T Cells Provide Help for B Cell Clonal Expansion and Antibody Synthesis in a Similar Manner In Vivo

“…Recent studies employing the adoptive transfer of TCR transgenic (tg) T cells have indicated that, in contrast to Th2 cells, CCR7 expression on Th1 cells reduces their migration to follicles and hence their ability to help B cell responses in vivo (21). However, Th2 cells may not be essential for B cell proliferation and differentiation, as IL-4 or IL-5 knockout (KO) mice, which have deficient Th2 responses, have readily detectable Ab production and germinal center formation (22)(23)(24). Furthermore, whereas Th1 cells are associated with cell-mediated immunity, and generally regarded as less important for B cell responses, IgG2a isotype switching is promoted by IFN-␥ (20,25,26), the prototypical Th1 cytokine.…”