Abnormal behavior of gamma-committed B lymphocytes probed by a lymphocyte blastogenesis inhibitory factor in autoimmune MRL mice.
Recently, we have characterized a lymphocyte blastogenesis inhibitory factor (LBIF) which was purified from the culture supernatant of a human histiocytic lymphoma U-937 (Sugimura, K. et al., Eur. J. Immunol. 1989. 19: 1357). In this study, we investigated the effect of LBIF on the antibody production of autoimmune MRL mice in vitro. We demonstrated here that (a) LBIF inhibited the IgM, IgG and IgA antibody responses of lipopolysaccharide (LPS)-stimulated spleen cells of normal BALB/c mice, (b) in the case of old autoimmune MRL/Mp-lpr/lpr (MRL/l) and MRL/Mp-(+)/+ mice, however, LBIF inhibited IgM and IgA but not IgG responses of LPS-stimulated spleen cells, (c) the antibody production of all IgG subclasses, IgG3, IgG1, IgG2b and IgG2a, was not sensitive to LBIF inhibitory activity in these autoimmune mice, (d) in young MRL mice (3-5-week-old MRL/l), which were phenotypically normal, LPS-induced antibody production of all isotypes (IgM, IgG and IgA) was strongly inhibited by LBIF as shown in normal BALB/c mice and (e) in the case of 7-week-old MRL/l the insensitivity to LBIF was concomitant with the appearance of gamma + B lymphocytes. Thus, by employing LBIF as a probe, this study showed a correlation between the pathogenesis of MRL autoimmune disease and the lack of LBIF sensitivity of hyperactive B lymphocytes and suggested that the intrinsic abnormality of autoimmune MRL B lymphocytes might be confined to gamma- but not mu- or alpha-committed B cells.
Sugimura
K
K
Institute of Immunological Science, Hokkaido University, Sapporo, Japan.
Wada
Y
Y
Kimura
T
T
Ohno
T
T
Kobayashi
S
S
Azuma
I
I
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D005260:Female; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007075:Immunoglobulin M / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008222:Lymphokines / Q000494:pharmacology*; D008232:Lymphoproliferative Disorders / Q000209:etiology / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C
D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; D008222:Lymphokines