RESUMO
The TNF superfamily cytokine BAFF has crucial roles in homoeostatic regulation of B cell populations in mammals. Similar effects on peripheral B cells have been reported for chicken as for mammalian BAFF. Unlike mammalian BAFF, chicken BAFF is produced by B cells, implying an autocrine loop and consequent differences in regulation of B cell homoeostasis. Understanding of these mechanisms requires investigation of BAFF-binding receptors in chickens. We identified and characterised chicken receptors BAFFR and TACI, but found that the gene encoding the third BAFF-binding receptor, BCMA, was disrupted, implying differences in mechanisms for maintenance of long-lived antibody responses. A BAFFR-Ig fusion protein expressed in vivo lowered B cell numbers, showing that it was functional under physiological conditions. We found changes in the ratio of BAFFR and TACI mRNAs in the bursa after hatch that may account for the altered requirements for B cell survival at this stage of development.
Assuntos
Receptor do Fator Ativador de Células B/metabolismo , Linfócitos B/imunologia , Bolsa de Fabricius/imunologia , Proteína Transmembrana Ativadora e Interagente do CAML/metabolismo , Sequência de Aminoácidos , Animais , Bolsa de Fabricius/citologia , Linhagem Celular , Embrião de Galinha , Galinhas , Humanos , Camundongos , Dados de Sequência Molecular , Proteínas Recombinantes de Fusão/metabolismo , Alinhamento de Sequência , Proteína Transmembrana Ativadora e Interagente do CAML/químicaRESUMO
Previous studies of cattle MHC have suggested the presence of at least four classical class I loci. Analysis of haplotypes showed that any combination of one, two or three genes may be expressed, although no gene is expressed consistently. The aim of this study was to examine the evolutionary relationships among these genes and to study their phylogenetic history in Cetartiodactyl species, including cattle and their close relatives. A secondary aim was to determine whether recombination had occurred between any of the genes. MHC class I data sets were generated from published sequences or by polymerase chain reaction from cDNA. Phylogenetic analysis revealed that MHC class I sequences from Cetartiodactyl species closely related to cattle were distributed among the main cattle gene "groups", while those from more distantly related species were either scattered (sheep, deer) or clustered in a species-specific manner (sitatunga, giraffe). A comparison between gene and species trees showed a poor match, indicating that divergence of the MHC sequences had occurred independently from that of the hosts from which they were obtained. We also found two clear instances of interlocus recombination among the cattle MHC sequences. Finally, positive natural selection was documented at positions throughout the alpha 1 and 2 domains, primarily on those amino acids directly involved in peptide binding, although two positions in the alpha 3 domain, a region generally conserved in other species, were also shown to be undergoing adaptive evolution.