Characterization of a functional null cell line derived from NZB x NZW)F1 mice.
We attempted to establish a null cell line from NZB x NZW(B/W)F1 mice in order to investigate a regulatory role of null cells during polyclonal B cell activation in autoimmune diseases. NB2.2, a representative subclone of resulting null cell lines, was maintained in long-term tissue culture with 10% mouse ConA supernatant (MCAS). Interestingly, the cell free supernatant of the NB2.2 cells (NB-CFS) showed marked synergistic effects on IgM secretion by B cells induced by IL-5. In addition, NB-CFS had the ability to augment the production of autoantibodies against bromelain-treated mouse red blood cells (BrMRBC) and single-stranded DNA (ssDNA) by B cells induced by IL-5. To determine whether NB2.2 cells induce polyclonal B cell activation and autoantibody generation in vivo, BALB/c mice were injected with NB2.2 cells. The results showed that the level of anti-ssDNA antibodies in sera of BALB/c mice injected with NB2.2 cells was significantly higher than that of control BALB/c mice injected with FDC-P2 cells. In addition, splenic B cells from mice injected with NB2.2 cells significantly proliferated in vitro in response to IL-4 and IL-5, and produced anti-ssDNA antibodies in the presence of IL-5. These results suggest that NB2.2, a null cell line established from B/WF1 mice, produces mediators capable of promoting polyclonal B cell activation and inducing autoantibody secretion, and that this kind of null cell may play an important role in the pathogenesis of autoimmune diseases.
Iwasaki
T
T
Second Department of Internal Medicine, Hyogo College of Medicine, Japan.
Hamano
T
T
Aizawa
K
K
Kobayashi
K
K
Kakishita
E
E
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000276:immunology; D002460:Cell Line; D017077:Culture Media, Conditioned; D004277:DNA, Single-Stranded / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006462:Hemolytic Plaque Technique; D007075:Immunoglobulin M / Q000096:biosynthesis; D015848:Interleukin-5 / Q000502:physiology; D008213:Lymphocyte Activation / Q000276:immunology; D008215:Lymphocytes, Null / Q000276:immunology*; D051379:Mice; D008814:Mice, Inbred NZB; D008815:Mice, Inbred Strains; D013154:Spleen / Q000166:cytology
D000974:Antibodies, Antinuclear; D017077:Culture Media, Conditioned; D004277:DNA, Single-Stranded; D007075:Immunoglobulin M; D015848:Interleukin-5