RESUMO
In mice the majority of the immunoglobulins (Ig) in milk belongs to the IgA class. Prior to its transepithelial transportation into the milk, dimeric IgA (dIgA) is bound to the transmembrane form of the secretory component or polymeric Ig receptor (SC/pIgR). The latter is synthesized in the epithelial cells lining the ducts and alveoli of the mammary gland. A candidate for playing the role of adhesion molecule to primed lymphocytes present in the murine mammary gland might be the mucosal addressin cell adhesion molecule-1 (MAdCAM-1). We studied the correlation between the levels of IgA in colostrum and milk, the number of IgA producing plasma cells in the mammary gland and the expression of MAdCAM-1 in mammary gland endothelial cells during pregnancy and lactation. The relation between the IgA levels in the milk and the expression levels of pIgR in mammary gland epithelial cells was also investigated. We found that the expression of MAdCAM-1 and pIgR starts in early-mid pregnancy; the number of IgA-producing plasma cells and the IgA concentration in milk increase from early lactation onwards. The MAdCAM-1 expression declines during lactation whereas the pIgR levels and IgA-producing plasma cell numbers rise until the end of lactation. Because the MAdCAM-1 level starts to rise several days before the rise of the IgA-producing plasma cell level, MAdCAM-1 cannot be the rate determining factor governing extravasation of primed B cells to the mammary gland. We also conclude that the pIgR is present in sufficient amounts to enable increasing S-IgA secretion into the milk during lactation.
Assuntos
Imunoglobulina A/análise , Imunoglobulinas/metabolismo , Glândulas Mamárias Animais/imunologia , Glândulas Mamárias Animais/metabolismo , Mucoproteínas/metabolismo , Receptores de Retorno de Linfócitos/metabolismo , Animais , Moléculas de Adesão Celular , Colostro/imunologia , Feminino , Imunoglobulinas/genética , Lactação/imunologia , Glândulas Mamárias Animais/crescimento & desenvolvimento , Camundongos , Camundongos Endogâmicos BALB C , Leite/imunologia , Mucoproteínas/genética , Plasmócitos/imunologia , Gravidez , RNA Mensageiro/biossíntese , Receptores de Retorno de Linfócitos/genética , Receptores de Imunoglobulina Polimérica/biossíntese , Receptores de Imunoglobulina Polimérica/genética , Componente Secretório/análiseRESUMO
The polymeric Ig receptor (pIgR) and J chain molecules are involved in the transfer of IgA across the mammary gland epithelia into milk. The J chain binds two IgA molecules to form dimeric IgA, and the pIgR transports this complex through epithelial cells. We report here the cloning of the first marsupial homologues for the pIgR and J chain from the brushtail possum. Marsupial young are born after a short gestation and are less developed than eutherian newborn. The pouch young is completely dependent on milk as its sole source of nutrition during early lactation and this phase can be considered to be equivalent to an external gestation. Two periods of increased expression of pIgR, J chain, and IgA heavy chain mRNAs were observed in the mammary gland during lactation. The first occurs for a brief period after birth of the pouch young and is likely to reflect IgA transfer via the colostrum. The second period of increased expression, which is unique to marsupials, occurs after the early lactation period and just before young exit the pouch. We propose that this represents a second colostral-like phase at the end of the external gestation.
Assuntos
Imunidade Materno-Adquirida , Imunoglobulina A/biossíntese , Lactação/imunologia , Gambás/imunologia , Receptores de Imunoglobulina Polimérica/biossíntese , Sequência de Aminoácidos , Animais , Sequência de Bases , Clonagem Molecular , Colostro/imunologia , Feminino , Imunoglobulina A/genética , Cadeias Pesadas de Imunoglobulinas/genética , Cadeias J de Imunoglobulina/genética , Região Variável de Imunoglobulina/genética , Glândulas Mamárias Animais/imunologia , Dados de Sequência Molecular , Gravidez , RNA Mensageiro/isolamento & purificação , Receptores de Imunoglobulina Polimérica/genética , Análise de Sequência de DNA , Homologia de Sequência de AminoácidosRESUMO
Mouse polymeric immunoglobulin receptor (pIgR) cDNA was stably introduced into a hamster-derived fibroblastic cell line, Chinese hamster ovary (CHO) cell, by the calcium phosphate method. Surface expression of pIgR was detected by immunostaining and FACS analysis. The immunoprecipitated products of cell lysates revealed that the molecular mass of the most mature form of pIgR was approximately 120 kDa. Western blotting and metabolic labeling experiments followed by immunoprecipitation with an anti-mouse secretory component (SC) Ab demonstrated the existence of a 110 kDa immature form of pIgR. The reason for the existence of two forms of pIgR molecule was examined by conducting pulse-chase experiments which revealed the pIgR underwent molecular maturation. During this process, the 110 kDa form of pIgR was converted into a 120 kDa form by glycosylation. Moreover, tunicamycin treatment revealed the core form of pIgR had a molecular mass of approximately 100 kDa. The pIgR expressed on the surface of the transfectant could specifically bind and take up mouse polymeric IgA (MOPC 315), suggesting that, at least in this mouse system, cell type-specific molecules are not necessary for surface pIgR expression and polymeric immunoglobulin (pIg) binding and uptake.