Prolactin levels correlate with abnormal B cell maturation in MRL and MRL/lpr mouse models of systemic lupus erythematosus-like disease.
Prolactin (PRL) plays an important role in modulating the immune response. In B cells, PRL enhances antibody production, including antibodies with self-specificity. In this study, our aims were to determine the level of PRL receptor expression during bone-marrow B-cell development and to assess whether the presence of high PRL serum concentrations influences absolute numbers of developing populations and disease outcome in lupus-prone murine models. We observed that the PRL-receptor is expressed in early bone-marrow B-cell; the expression in lupus-prone mice, which had the highest level of expression in pro-B cells and immature cells, differed from that in wild-type mice. These expression levels did not significantly change in response to hyperprolactinemia; however, populations of pro-B and immature cells from lupus-prone strains showed a decrease in the absolute numbers of cells with high PRL-receptor expression in response to PRL. Because immature self-reactive B cells are constantly being eliminated, we assessed the expression of survival factor BIRC5, which is more highly expressed in both pro-B and immature B-cells in response to PRL and correlates with the onset of disease. These results identify an important role of PRL in the early stages of the B-cell maturation process: PRL may promote the survival of self-reactive clones.
UIM en Inmunología, Hospital de Pediatría, CMN Siglo XXI, IMSS, 06720 Mexico City, DF, Mexico.
Maria Victoria
MV
Legorreta-Haquet
UIM en Inmunología, Hospital de Pediatría, CMN Siglo XXI, IMSS, 06720 Mexico City, DF, Mexico ; Departamento de Inmunología, ENCB, IPN, 11340 Mexico City, DF, Mexico.
Rocio
R
Flores-Fernández
UIM en Inmunología, Hospital de Pediatría, CMN Siglo XXI, IMSS, 06720 Mexico City, DF, Mexico.
Francisco
F
Blanco-Favela
Unidad de Investigación en Virología y Cáncer Hospital Infantil de México Federico Gómez, 06720 Mexico City, DF, Mexico.
Ezequiel M
EM
Fuentes-Pananá
UIM en Inmunología, Hospital de Pediatría, CMN Siglo XXI, IMSS, 06720 Mexico City, DF, Mexico.
Luis
L
Chávez-Sánchez
Departamento de Investigación Experimental y Bioterio del Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", 14000 Mexico City, DF, Mexico.
Rafael
R
Hernández-González
UIM en Inmunología, Hospital de Pediatría, CMN Siglo XXI, IMSS, 06720 Mexico City, DF, Mexico ; Departamento de Investigación Experimental y Bioterio del Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", 14000 Mexico City, DF, Mexico.
Emiliano
E
Tesoro-Cruz
UIM en Inmunoquímica, Hospital de Especialidades, CMN Siglo XXI, IMSS, 06720 Mexico City, DF, Mexico.
Lourdes
L
Arriaga-Pizano
UIM en Inmunología, Hospital de Pediatría, CMN Siglo XXI, IMSS, 06720 Mexico City, DF, Mexico.
Adriana Karina
AK
Chávez-Rueda
D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006966:Hyperprolactinemia / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016130:Immunophenotyping; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D018655:Lymphocyte Count; D051379:Mice; D019463:Mice, Inbred MRL lpr; D011388:Prolactin / Q000097:blood / Q000378:metabolism*; D011981:Receptors, Prolactin / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D000077022:Survivin
D000974:Antibodies, Antinuclear; C117749:Birc5 protein, mouse; D051034:Inhibitor of Apoptosis Proteins; D011981:Receptors, Prolactin; D012097:Repressor Proteins; D000077022:Survivin; D011388:Prolactin