Open Access Research article

Increased levels of prolactin receptor expression correlate with the early onset of lupus symptoms and increased numbers of transitional-1 B cells after prolactin treatment

Yadira Ledesma-Soto15, Francisco Blanco-Favela1, Ezequiel M Fuentes-Pananá2, Emiliano Tesoro-Cruz13, Rafael Hernández-González3, Lourdes Arriaga-Pizano4, María V Legorreta-Haquet1, Eduardo Montoya-Diaz1, Luis Chávez-Sánchez1, María E Castro-Mussot5 and Adriana K Chávez-Rueda1*

Author Affiliations

1 Unidad de Investigación Médica en Inmunología, Hospital de Pediatría, CMN Siglo XXI, IMSS. Av Cuauhtemoc 330. Col. Doctores, Mexico, D.F. CP06720, Mexico

2 Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias, Hospital de Pediatría, CMN Siglo XXI, IMSS. Av Cuauhtemoc 330. Col. Doctores, Mexico, D.F., Mexico

3 Departamento de Investigación Experimental y Bioterio del Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Vasco de Quiroga 15, Col Tlalpan, Mexico, D.F., Mexico

4 Unidad de Investigación Médica en Inmunoquímica, Hospital de Especialidades, CMN Siglo XXI, IMSS. Av Cuauhtemoc 330. Col. Doctores, Mexico, D.F., Mexico

5 Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, IPN. Prolongación de Carpio y Plan de Ayala s/n Col. Santo Tomas., Mexico D.F., Mexico

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BMC Immunology 2012, 13:11  doi:10.1186/1471-2172-13-11

Published: 9 March 2012

Abstract

Background

Prolactin is secreted from the pituitary gland and other organs, as well as by cells such as lymphocytes. Prolactin has an immunostimulatory effect and is associated with autoimmune diseases that are characterised by abnormal B cell activation, such as systemic lupus erythematosus (SLE). Our aim was to determine if different splenic B cell subsets express the prolactin receptor and if the presence of prolactin influences these B cell subsets and correlates with development of lupus.

Results

Using real-time PCR and flow cytometry, we found that different subsets of immature (transitional) and mature (follicular, marginal zone) B cells express different levels of the prolactin receptor and are differentially affected by hyperprolactinaemia. We found that transitional B cells express the prolactin receptor at higher levels compared to mature B cells in C57BL/6 mice and the lupus-prone MRL/lpr and MRL mouse strains. Transitional-1 (T1) B cells showed a higher level of prolactin receptor expression in both MRL/lpr and MRL mice compared to C57BL/6 mice. Hyperprolactinaemia was induced using metoclopramide, which resulted in the development of early symptoms of SLE. We found that T1 B cells are the main targets of prolactin and that prolactin augments the absolute number of T1 B cells, which reflects the finding that this B cell subpopulation expresses the highest level of the prolactin receptor.

Conclusions

We found that all B cell subsets express the prolactin receptor but that transitional B cells showed the highest prolactin receptor expression levels. Hyperprolactinaemia in mice susceptible to lupus accelerated the disease and increased the absolute numbers of T1 and T3 B cells but not of mature B cells, suggesting a primary effect of prolactin on the early stages of B cell maturation in the spleen and a role of prolactin in B cell differentiation, contributing to SLE onset.