RESUMEN
Secretory immunoglobulin A (SIgA) enhances host-microbiota symbiosis, whereas SIgM remains poorly understood. We found that gut IgM+ plasma cells (PCs) were more abundant in humans than mice and clonally related to a large repertoire of memory IgM+ B cells disseminated throughout the intestine but rare in systemic lymphoid organs. In addition to sharing a gut-specific gene signature with memory IgA+ B cells, memory IgM+ B cells were related to some IgA+ clonotypes and switched to IgA in response to T cell-independent or T cell-dependent signals. These signals induced abundant IgM which, together with SIgM from clonally affiliated PCs, recognized mucus-embedded commensals. Bacteria recognized by human SIgM were dually coated by SIgA and showed increased richness and diversity compared to IgA-only-coated or uncoated bacteria. Thus, SIgM may emerge from pre-existing memory rather than newly activated naive IgM+ B cells and could help SIgA to anchor highly diverse commensal communities to mucus.
Asunto(s)
Angiodisplasia/inmunología , Linfocitos B/inmunología , Neoplasias del Colon/inmunología , Pólipos del Colon/inmunología , Inmunoglobulina M/metabolismo , Intestinos/inmunología , Células Plasmáticas/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Animales , Células Clonales , Femenino , Microbioma Gastrointestinal/inmunología , Humanos , Inmunidad Mucosa , Inmunoglobulina A/metabolismo , Cambio de Clase de Inmunoglobulina , Memoria Inmunológica , Intestinos/microbiología , Masculino , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , SimbiosisRESUMEN
A patient with a severe bleeding tendency due to acquired von Willebrand disease (VWD) is presented. Although no underlying disorder has emerged during 6 years of follow-up, an immune-mediated mechanism was responsible for acquired VWD in this patient as demonstrated by detection of von Willebrand factor (VWF)/anti-VWF complexes in the patient's plasma and their removal by protein A-sepharose beads and resumption of normal haemostasis with correction of VWF antigen, VWF activity and VWF multimeric pattern after treatment of the patient with high-dose gammaglobulin. Detection of anti-VWF antibodies in the patient's plasma had a significant impact on the choice of therapeutic intervention to control bleeding.