β Scribed by Padmalatha S. Reddy; Ronald B. Corley
No coin nor oath required. For personal study only.
mmunoglobulin M (IgM) is the first antibody that is produced in the immune system and plays an important role in primary and adaptive humoral immune responses (Table ). IgM comprises a significant fraction of 'natural' antibodies, many of which are multireactive and bind determinants found on the membranes of bacterial and viral pathogens . IgM provides a crucial first line of defense for the immune system, and its ability to agglutinate pathogens enhances phagocytosis and clearance. IgM also efficiently activates complement, especially when bound to cellular antigens, and this further facilitates pathogen opsonization. Complement components are important mediators that link the innate and adaptive immune systems 3 .
IgM also plays important roles in adaptive humoral immune responses. IgM has the unique capacity to enhance immune responses specifically against particulate antigens 4 . The efficiency with which IgM activates complement is crucial for its enhancing activity 5 . Complement components, especially C3d, increase the deposition of immune complexes on complement-receptor positive cells, including B cells and follicular dendritic cells (FDC), and this serves to amplify the immune response 3 . Complement-containing complexes can also stimulate the survival of CD5 Ο© B1 B cells, which are believed to produce a significant fraction of natural IgM to pathogens 3 . This suggests the existence of a positive feedback loop that maintains the levels of natural IgM antibodies of various specificities. Finally, IgM can participate in mucosal immunity, as joining (J)-chain-containing polymers can be transcytosed across epithelial surfaces by virtue of their interaction with the polyimmunoglobulin receptor .
The central role of secretory IgM in the immune response is supported by studies of IgM-deficient mice. Mice with mutations in the Bruton's tyrosine kinase (Btk Οͺ/Οͺ ) have very low levels of IgM and exhibit selective immunodeficiencies in immune responses to polysaccharides and various pathogens 7 . IgM Οͺ/Οͺ mice that lack both membrane and secretory IgM are more susceptible to pathogens than their wild-type counterparts, owing, at least in part, to the delayed production of neutralizing antibodies 8 . Studies of mice that lack only secretory IgM show that they do not respond well to T-dependent antigens, and that they are not as competent as IgM sufficient mice to respond to certain pathogens . This deficit can be attributed to diminished antigen trapping on FDC and impaired germinal center formation. Overall, secretory IgM carries out unique and important roles that 70
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