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Prolactin modulates the naive B cell repertoire
Elena Peeva1, Daniel Michael, James Cleary
1Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
The Journal of Clinical Investigation
|January 18, 2003
Summary
Prolactin, a hormone, can trigger a lupus-like autoimmune response in susceptible mice by affecting B cell populations and increasing anti-DNA antibodies. This immune system response to prolactin is genetically influenced.
Area of Science:
- Immunology
- Endocrinology
- Autoimmunity
Background:
- Prolactin (PRL) is a pituitary hormone crucial for lactation.
- Lymphocytes also produce prolactin and express prolactin receptors, suggesting immunomodulatory roles.
- Previous studies link prolactin to augmented autoreactivity in autoimmune models.
Purpose of the Study:
- To investigate the specific effects of prolactin on anti-DNA B cells in a non-spontaneously autoimmune mouse model.
- To determine if prolactin can induce an autoimmune phenotype, specifically a lupus-like condition.
Main Methods:
- BALB/c mice transgenic for anti-DNA antibody heavy chains were treated with prolactin for 4 weeks.
- Flow cytometry and serological analyses were used to assess B cell populations, autoantibody titers, and immune complex deposition.
- Analysis of B cell repertoire selection and T cell dependency was performed.
Main Results:
- Prolactin treatment induced a lupus-like phenotype, characterized by increased transgene-expressing B cells, elevated anti-DNA antibody titers, and glomerular immunoglobulin deposits.
- Prolactin altered B cell populations, decreasing transitional B cells and increasing mature follicular and marginal zone B cells.
- Expansion of anti-DNA B cells was CD4(+) T cell-dependent and influenced naive B cell repertoire selection.
- Tolerance was not broken in C57Bl/6 mice, indicating genetic determination of prolactin responsiveness.
Conclusions:
- Prolactin can promote the development of a lupus-like autoimmune disease in genetically susceptible individuals.
- Prolactin influences B cell development, activation, and repertoire selection, contributing to autoreactivity.
- The immune system's response to prolactin is genetically controlled, highlighting the importance of host factors in autoimmunity.