Increased autoantibody production by NZB/NZW B cells in response to IL-5.
We previously demonstrated that B cells from NZB/NZW but not nonautoimmune mice secrete high levels of autoantibodies in response to factor(s) derived from type 2 Th cell (Th2) clones. Supernatants from type 1 Th cell clones, which contain a different set of lymphokines, were not stimulatory. In the present experiments, we attempted to define the active Th2 factor(s) and to better understand the cellular basis for the hyperresponsiveness. In response to optimal concentrations of supernatant (Th2-Sup), B cells from 3-mo-old NZB/NZW mice produced up to 40-fold greater amounts of IgM anti-DNA compared with unstimulated B cells, whereas BALB/c B cells produced levels only slightly above background. Although Th2-Sup contained large amounts of IL-4, comparable concentrations of rIL-4 alone did not stimulate NZB/NZW B cells. Furthermore, a blocking anti-IL-4 mAb did not prevent Th2-Sup-stimulated autoantibody production. Th2-Sup was fractionated by HPLC, and the stimulatory factor(s) was found in fractions known to contain IL-5 (also known as B cell growth factor II). Indeed, a highly purified preparation of IL-5 reproduced the effects of Th2-Sup by stimulating NZB/NZW B cells to produce high levels of IgM anti-DNA antibodies while enhancing production by nonautoimmune cells only slightly. In limiting dilution studies, NZB/NZW compared with BALB/c spleens contained a three- to four-fold greater frequency of DNA-specific B cells that were responsive to IL-5. Together, the results suggest a potential role for IL-5 in the pathogenesis of NZB/NZW autoimmune disease.
Herron
L R
LR
Department of Medicine, Veterans Administration Medical Center, Denver, Colorado 80220.
Coffman
R L
RL
Bond
M W
MW
Kotzin
B L
BL
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D001323:Autoantibodies / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002474:Cell-Free System; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D015847:Interleukin-4; D015848:Interleukin-5; D007378:Interleukins / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008814:Mice, Inbred NZB; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D015848:Interleukin-5; D007378:Interleukins; D015847:Interleukin-4