B cell hyperresponsiveness to interleukin 2 and the age-associated decline in murine lupus.
In young NZB x NZW (B/W) F1 mice there was a population of B cells that were hyperresponsive to interleukin 2 (IL-2) and that proliferated but did not differentiate, even in the absence of a prior activation signal, and hence were already stimulated in vivo and were prepared to respond to IL-2. These B cells belonged to the population that was nonadherent to the Sephadex G-10 (G-10) column. We found that such hyperresponsiveness was progressively reduced with the aging of these mice. This event did not appear to be related to the age-associated changes of IL-2 receptors on B cells, since the IL-2-binding ability and the density of IL-2 receptor alpha expressed on B cells in culture did not differ between the young and the old mice. Studies suggested that two major mechanisms are responsible for the age-associated decline in the IL-2 responsiveness of B cells. First, the capacity of IL-2 hyperresponsiveness of such B cells decreases in B/W F1 mice with aging, probably through further activation and differentiation of the B cells. Second, the G-10 adherent, but not nonadherent, B cells from the aged mice inhibit the IL-2 response of G-10 nonadherent B cells. The G-10 adherent B cells from the old mice also inhibited the IL-2 production of T cells from the young B/W F1 mice. Taken together, it appears that young B/W F1 mice bear a population of B cells already stimulated so that they can respond to IL-2 without prior stimuli. With aging, activation of the B cells progresses and they appear to down-regulate the IL-2 hyperresponse of B cells and the IL-2 synthesis by T cells.
Sekigawa
I
I
Department of Pathology, Juntendo University School of Medicine, Tokyo, Japan.
Noguchi
K
K
Hasegawa
K
K
Hirose
S
S
Sato
H
H
Shirai
T
T
D000375:Aging / Q000276:immunology; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008814:Mice, Inbred NZB; D015375:Receptors, Interleukin-2 / Q000032:analysis
D007376:Interleukin-2; D015375:Receptors, Interleukin-2