B cell hyperactivity in autoimmune continuous B cell lines

Generalized increase in immunoglobulin secretion, which is a prominent feature of autoimmune diseases, may be due to abnormal T cell regulation, intrinsic abnormality of B cells, or both. To investigate this question we developed nonmalignant continuous B lymphocyte lines from 20-week-old BWF1 mice and compared their growth and immune response to that of BALB/c mice cell lines. The B cell lines contain less than 1% T cells and macrophages and require growth factors from phytohemagglutinin-stimulated EL-4 lymphoma (GF) or recombinant interleukin 4 for continuous growth. No antigens or mitogens are required for growth. In the presence of 20% GF (which is optimal for BALB/c cell growth and immune function) spontaneous growth of BWF1 B cells, and spontaneous entry into G1, was similar to that of BALB/c B cells. With concentrations of GF and anti-mu which were optimal for BALB/c, the growth and immune response of isolated BWF1 B cells are no different from those of BALB/c controls, but at suboptimal doses of GF there is a significant increase of both spontaneous immunoglobulin secretion and response to anti-mu in BWF1 B cells. Thus, these autoimmune B cells are more sensitive to the effects of both T cell factors and immunoglobulin receptors stimulation.