Responses of B cells from autoimmune mice to IL-5.
Three strains of mice (NZB/W F1 X NZW (NZB/W), BXSB, and MRL/Mp-lpr/lpr (MRL/lpr] develop an autoimmune disease that is clinically and immunologically similar to human SLE. A characteristic of these mice is polyclonal B cell hyperactivity. To explore whether this may be related to hyper-responsiveness to B cell stimulatory factors, we investigated the proliferative and secretory responses of B cells from these mice to semi-purified natural and rIL-5, a major regulator of B cell development in the mouse. As this lymphokine stimulates growth and differentiation of activated B cells, attention was focused on in vivo-activated B cell populations, obtained from the interface of 50/65% Percoll density gradients, from normal or autoimmune mice. This cell population from NZB/W mice secreted IgM and incorporated [3H]TdR at significantly higher levels in response to IL-5, and was more sensitive to IL-5, than a comparable population from several normal murine strains. NZB/W female and male mice displayed heightened responses to IL-5, indicating that this is characteristic of the strain in general and is not associated with the accelerated severe disease of the females. Small resting B cells from NZB/W and normal mice were insensitive to IL-5 stimulation. In contrast to NZB/W mice, no difference was observed in the magnitude of either proliferative or Ig secretory responses between in vivo-activated B cell populations from autoimmune BXSB and MRL/lpr or normal mice. Thus, B cell hyper-responsiveness to IL-5 is a characteristic of NZB/W mice but not of two other lupus-prone murine strains. As one unique feature of NZB/W mouse B cells compared to normal and other autoimmune B cells is an elevated proportion of Ly-1+ B cells, the possibility of IL-5 hyper-responsiveness being associated with this B cell subpopulation was investigated. Fluorescence-activated cell sorter sorted Ly-1+ and Ly-1- B cells both responded to IL-5, however Ly-1+ B cells consistently showed a higher stimulation index in both proliferative and Ig secretory responses to this lymphokine.
Umland
S P
SP
DNAX Research Institute of Cellular and Molecular Biology, Palo Alto, CA 94304-1104.
Go
N F
NF
Cupp
J E
JE
Howard
M
M
D000818:Animals; D000950:Antigens, Ly; D001327:Autoimmune Diseases / Q000276:immunology*; D001402:B-Lymphocytes / Q000145:classification / Q000276:immunology* / Q000378:metabolism; D002469:Cell Separation; D005260:Female; D007136:Immunoglobulins / Q000096:biosynthesis; D015848:Interleukin-5; D007378:Interleukins / Q000494:pharmacology*; D007399:Interphase / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D008814:Mice, Inbred NZB; D010641:Phenotype; D013045:Species Specificity; D013601:T-Lymphocytes
D000950:Antigens, Ly; D007136:Immunoglobulins; D015848:Interleukin-5; D007378:Interleukins