Asunto(s)
Insuficiencia Renal Crónica , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Riñón/efectos de los fármacos , Riñón/fisiología , Riñón/fisiopatología , Insuficiencia Renal Crónica/tratamiento farmacológico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacologíaAsunto(s)
Infecciones por HTLV-I/genética , Virus Linfotrópico T Tipo 1 Humano/inmunología , Enfermedades de Transmisión Sexual/genética , Australia/epidemiología , Infecciones por HTLV-I/inmunología , Infecciones por HTLV-I/transmisión , Infecciones por HTLV-I/virología , Virus Linfotrópico T Tipo 1 Humano/genética , Virus Linfotrópico T Tipo 1 Humano/patogenicidad , Humanos , Enfermedades de Transmisión Sexual/inmunología , Enfermedades de Transmisión Sexual/virología , Estados Unidos/epidemiologíaAsunto(s)
Control de Enfermedades Transmisibles/métodos , Enfermedades Transmisibles/inmunología , Interacciones Huésped-Patógeno , Orthomyxoviridae/fisiología , Antivirales/farmacología , Humanos , Vacunas contra la Influenza/administración & dosificación , Orthomyxoviridae/efectos de los fármacos , Orthomyxoviridae/inmunologíaRESUMEN
Infection with Staphylococcus aureus does not induce long-lived protective immunity for reasons that are not completely understood. Human and murine vaccine studies support a role for Abs in protecting against recurring infections, but S. aureus modulates the B cell response through expression of staphylococcus protein A (SpA), a surface protein that drives polyclonal B cell expansion and induces cell death in the absence of costimulation. In this murine study, we show that SpA altered the fate of plasmablasts and plasma cells (PCs) by enhancing the short-lived extrafollicular response and reducing the pool of bone marrow (BM)-resident long-lived PCs. The absence of long-lived PCs was associated with a rapid decline in Ag-specific class-switched Ab. In contrast, when previously inoculated mice were challenged with an isogenic SpA-deficient S. aureus mutant, cells proliferated in the BM survival niches and sustained long-term Ab titers. The effects of SpA on PC fate were limited to the secondary response, because Ab levels and the formation of B cell memory occurred normally during the primary response in mice inoculated with wild-type or SpA-deficient S. aureus mutant. Thus, failure to establish long-term protective Ab titers against S. aureus was not a consequence of diminished formation of B cell memory; instead, SpA reduced the proliferative capacity of PCs that entered the BM, diminishing the number of cells in the long-lived pool.
Asunto(s)
Células Plasmáticas/efectos de los fármacos , Proteína Estafilocócica A/farmacología , Animales , Células Productoras de Anticuerpos/inmunología , Inmunoglobulina G/biosíntesis , Memoria Inmunológica , Interleucina-12/biosíntesis , Ratones , Ratones Endogámicos C57BL , Células Plasmáticas/inmunología , Bazo/inmunología , Staphylococcus aureus/inmunologíaAsunto(s)
Aprobación de Drogas , Industria Farmacéutica/tendencias , Preparaciones Farmacéuticas , Ensayos Clínicos como Asunto , Descubrimiento de Drogas , Quimioterapia , Europa (Continente) , Terapia Genética , Política de Salud , Humanos , Atrofia Muscular Espinal/tratamiento farmacológico , Nucleótidos/química , Estados Unidos , United States Food and Drug AdministrationAsunto(s)
Adenocarcinoma/patología , Plasticidad de la Célula , Transformación Celular Neoplásica , Células Neuroendocrinas/patología , Fenotipo , Neoplasias de la Próstata Resistentes a la Castración/patología , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Humanos , Masculino , Células Neuroendocrinas/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/metabolismoRESUMEN
Memory B cell responses are vital for protection against infections but must also be regulated to prevent autoimmunity. Cognate T cell help, somatic hypermutation, and affinity maturation within germinal centers (GCs) are required for high-affinity memory B cell formation; however, the signals that commit GC B cells to the memory pool remain unclear. In this study, we identify a role for IgG-immune complexes (ICs), FcγRs, and BAFF during the formation of memory B cells in mice. We found that early secretion of IgG in response to immunization with a T-dependent Ag leads to IC-FcγR interactions that induce dendritic cells to secrete BAFF, which acts at or upstream of Bcl-6 in activated B cells. Loss of CD16, hematopoietic cell-derived BAFF, or blocking IC:FcγR regions in vivo diminished the expression of Bcl-6, the frequency of GC and memory B cells, and secondary Ab responses. BAFF also contributed to the maintenance and/or expansion of the follicular helper T cell population, although it was dispensable for their formation. Thus, early Ab responses contribute to the optimal formation of B cell memory through IgG-ICs and BAFF. Our work defines a new role for FcγRs in GC and memory B cell responses.