Session Information
Title: B cell Biology and Targets in Autoimmune Disease: Systemic Lupus Erythematosus and Related Diseases
Session Type: Abstract Submissions (ACR)
Background/Purpose
Prolactin (PRL) plays an important role in modulating the immune response. PRL is secreted by the pituitary gland as well as many other organs and cells, such as lymphocytes. In B cells, PRL enhances antibody production, including those with self-specificity; as such, PRL has been associated with B cell-triggered autoimmune diseases such as systemic lupus erythematosus (SLE). In this study, our aims were to determine the expression of PRL-receptor during bone marrow B cell development and whether the presence of high PRL serum concentration influences absolute numbers of developing populations and disease outcome in lupus-prone murine models.
Methods
All of the mice experiments were performed in accordance with approved guidelines established by Mexico (Norma Oficial Mexicana NOM-062-ZOO-1999). The NIH Guide for the Care and Use of Laboratory AnimalsC57BL/6 mice were purchased from Harlan, the MRL/MpJ (MRL) and MRL/MpJFASlpr(MRL/lpr) mice were purchased from the Jackson Laboratory. The pro-B, pre-B and immature B cells from the bone marrow of mice were purified by flow cytometry and were assayed for the expression of PRL receptor mRNA and protein. The nine weeks old mice were treated with metoclopramide for six weeks to induce high levels of PRL, accelerate SLE symptoms, and the absolute cell numbers of bone marrow B cell subsets were analysed.
Results
Using real time-PCR and flow cytometry, we observed that the PRL-receptor is expressed in bone marrow early B cells (pro-B, pre-B, immature); in lupus prone mice the highest level of expression was found in pro-Bs and immature cells. Immature cells from lupus-prone strains showed a decrease in the absolute numbers of cells with high PRL-receptor expression in response to PRL. Since immature B cells are permanently being subjected to anti-self-elimination mechanisms, we assessed the survival in immature B cell line and immature B cells from mice. Immature B cells incubated with an anti-IgM antibody have increased survival rates in hyperprolactinemic conditions, in the same way in immature B cells lines the mRNA expression of Bcl-xL was increased.
Conclusion
Taken together, these data indicate an important effect of PRL on B cell development, both favouring positive selection and counteracting mechanisms against self-specificity. In this scenario, increased PRL levels would result in the maturation of B cell clones with self-reactivity and an increased risk for developing auto-immune diseases
Disclosure:
K. Chavez-Rueda,
None;
R. Flores-Fernández,
None;
F. Blanco-Favela,
None;
M. Legorreta-Haquet,
None;
L. Chávez-Sánchez,
None;
R. Hernández-González,
None;
E. Tesoro-Cruz,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/prolactin-promotes-survival-of-immature-b-cells-from-mrllpr-mice/