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B cell hyperactivity in autoimmune continuous B cell lines
M Aldo-Benson1, M S Brooks, L Scheiderer-Pratt
1Department of Medicine, Indiana University School of Medicine, Indianapolis.
Immunologic Research
|January 1, 1989
Summary
Autoimmune B cells from BWF1 mice show increased immunoglobulin secretion, especially at suboptimal growth factor levels. These autoimmune B cells are more sensitive to T cell factors and immunoglobulin receptor stimulation.
Area of Science:
- Immunology
- Autoimmune Diseases
- Cell Biology
Background:
- Generalized increase in immunoglobulin secretion is characteristic of autoimmune diseases.
- This hypersecretion may stem from abnormal T cell regulation, intrinsic B cell abnormalities, or both.
- Investigating B cell intrinsic properties is crucial for understanding autoimmune disease pathogenesis.
Purpose of the Study:
- To investigate the intrinsic properties of B cells in autoimmune disease.
- To compare the growth and immune response of nonmalignant B lymphocyte lines from autoimmune-prone BWF1 mice with those from normal BALB/c mice.
- To determine if autoimmune B cells exhibit altered sensitivity to growth factors and receptor stimulation.
Main Methods:
- Developed nonmalignant, continuous B lymphocyte lines from 20-week-old BWF1 and BALB/c mice.
- B cell lines were maintained with growth factors (GF) from phytohemagglutinin-stimulated EL-4 lymphoma or recombinant interleukin 4.
- Compared spontaneous growth, immunoglobulin secretion, and response to anti-mu stimulation under varying GF concentrations.
Main Results:
- BWF1 and BALB/c B cells showed similar spontaneous growth and G1 entry at optimal GF concentrations.
- At optimal GF and anti-mu concentrations, BWF1 and BALB/c B cells exhibited comparable growth and immune responses.
- At suboptimal GF doses, BWF1 B cells displayed significantly increased spontaneous immunoglobulin secretion and enhanced response to anti-mu stimulation.
- This indicates autoimmune B cells are more sensitive to T cell factors and immunoglobulin receptor stimulation.
Conclusions:
- Autoimmune B cells possess an intrinsic hypersensitivity to both T cell-derived growth factors and B cell receptor stimulation.
- This heightened sensitivity contributes to the generalized increase in immunoglobulin secretion observed in autoimmune diseases.
- The findings highlight intrinsic B cell abnormalities as a key factor in autoimmune pathogenesis.
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