Prolactin Rescues Immature B-Cells from Apoptosis Induced by B-Cell Receptor Cross-Linking.
Prolactin has an immunomodulatory effect and has been associated with B-cell-triggered autoimmune diseases, such as systemic lupus erythematosus (SLE). In mice that develop SLE, the PRL receptor is expressed in early bone marrow B-cells, and increased levels of PRL hasten disease manifestations, which are correlated with a reduction in the absolute number of immature B-cells. The aim of this work was to determine the effect of PRL in an in vitro system of B-cell tolerance using WEHI-231 cells and immature B-cells from lupus prone MRL/lpr mice. WEHI-231 cells express the long isoform of the PRL receptor, and PRL rescued the cells from cell death by decreasing the apoptosis induced by the cross-linking of the B-cell antigen receptor (BCR) as measured by Annexin V and active caspase-3. This decrease in apoptosis may have been due to the PRL and receptor interaction, which increased the relative expression of antiapoptotic Bcl-xL and decreased the relative expression of proapoptotic Bad. In immature B-cells from MRL/lpr mice, PRL increased the viability and decreased the apoptosis induced by the cross-linking of BCR, which may favor the maturation of self-reactive B-cells and contribute to the onset of disease.
UIM en Inmunología, Hospital de Pediatría, CMN Siglo XXI, IMSS, 06720 Ciudad de México, DF, Mexico; Programa de Doctorado en Ciencias Biomédicas, UNAM, 04510 Ciudad de México, DF, Mexico.
Rocio
R
Flores-Fernández
UIM en Inmunología, Hospital de Pediatría, CMN Siglo XXI, IMSS, 06720 Ciudad de México, DF, Mexico.
Francisco
F
Blanco-Favela
Hospital Infantil de México Federico Gómez, Unidad de Investigación en Virología y Cáncer, 06720 Ciudad de México, DF, Mexico.
Ezequiel M
EM
Fuentes-Pananá
UIM en Inmunología, Hospital de Pediatría, CMN Siglo XXI, IMSS, 06720 Ciudad de México, DF, Mexico.
Luis
L
Chávez-Sánchez
Departamento de Investigación en Bioquímica, Instituto Nacional de Enfermedades Respiratorias "Ismael Cosió Villegas", 14080 Ciudad de México, DF, Mexico.
Patricia
P
Gorocica-Rosete
Unidad de Investigación y Bioterio, Instituto Nacional de Enfermedades Respiratorias "Ismael Cosió Villegas", 14080 Ciudad de México, DF, Mexico.
Alberto
A
Pizaña-Venegas
UIM en Inmunología, Hospital de Pediatría, CMN Siglo XXI, IMSS, 06720 Ciudad de México, DF, Mexico.
Adriana Karina
AK
Chávez-Rueda
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D015870:Gene Expression; D051379:Mice; D019463:Mice, Inbred MRL lpr; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D011981:Receptors, Prolactin / Q000235:genetics / Q000378:metabolism
D011947:Receptors, Antigen, B-Cell; D011981:Receptors, Prolactin; D011388:Prolactin; D053148:Caspase 3