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Biomedical subjects

M S Brooks

Publications and source records attributed to M S Brooks.

8 recordsLinked to original sources

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.

Animals

Defects in antigen-specific immune tolerance in continuous B cell lines from autoimmune mice.

B cell hyperactivity and resistance to tolerance induction are well-recognized immunologic abnormalities associated with both human and murine models of systemic lupus erythematosus. Studies evaluating the role of B cells in these defects have been complicated by the difficulties of consistently isolating large numbers of B cells from T cells and other host-derived regulatory factors. We have recently developed continuous cell lines of B lymphocytes with a high degree of specificity for the antigen dinitrophenyl (DNP) from both New Zealand black times New Zealand white F1 hybrid (BWF1) and BALB/c mice, and we used them to study intrinsic B cell defects in autoimmunity. We found that the kinetics of the immune response to the antigen DNP-Ficoll of both the BWF1 and BALB/c B cell lines are not different. In addition, the BWF1 cell lines, like the BALB/c cell lines and normal B cells, require nonspecific T cell-derived factors as well as antigen to produce an immune response. Tolerance was tested in the BWF1 B cells by preincubating them with DNP-murine IgG2a (MGG), which can induce tolerance in BALB/c cell line lymphocytes. The BWF1 B cell lines were resistant to tolerance induction by DNP-MGG and required 50-fold higher dose of DNP-MGG than BALB/c cell lines for suppression. They were also relatively resistant to tolerance with trinitrophenyl-d-glutamyl lysine. Thus, DNP-specific B cells from autoimmune mice have an inherent defect in tolerance induction.

Animals

Idiopathic fibrosclerosis.

Idiopathic fibrosclerosis (IF) is an acute and chronic inflammatory cellular infiltration of tissue associated with varying amounts of fibrosis. Clinical prototypes of IF include retroperitoneal fibrosis, mediastinal fibrosis and Reidel's struma of the thyroid. IF has been associated with numerous other diseases in the literature including systemic lupus erythematosus, scleroderma, polyarteritis nodosa and reactions to several drugs, especially, methysergide and several antihypertensive. However, no clear etiologic factor for either the inflammatory component or the fibrosis has been found. We present 2 cases of IF that exemplify the protean nature of the disease and its potential response to immunosuppressive therapy.

Adult