The immunoglobulin M or IgM is an antibody produced by B cells or lymphocytes of the immune system of many animals. It can be found attached to the plasma membrane of these cells or it can be secreted as a complex into the bloodstream and lymph, so it actively participates in the processes of humoral or adaptive immunity.
Like the other immunoglobulins (IgG, IgA, IgD and IgE), immunoglobulin M has such a structure that makes it capable of binding almost any type of antigen, including proteins, glycoproteins, polysaccharides and other carbohydrates, nucleic acids, lipids, among others.
Scheme of immunoglobulin M, a pentamer. Author: Artur Jan Fijałkowski, wikimedia commons
IgM is one of the first antibodies produced during the course of a bacterial infection and during neonatal development.
It was the first to be purified with significant homogeneity and since it is a poly-reactive antibody, that is, it has the ability to bind two or more antigens simultaneously even if they are different in nature, it is very important to combat different pathologies.
As “natural antibodies,” that is, those that are produced without prior intentional immunization, these immunoglobulins can bind not only to bacterial antigens, but also to viruses, protozoa, metazoan parasites, and fungi, as well as certain components of blood plasma.
Structure of IgM
Analogously to what has been described for immunoglobulin G, one of the most abundant antibodies in blood plasma, and the other immunoglobulins, the monomers of immunoglobulin M have a structure that could be described as in the form of a "Y", although this Antibody is usually found in plasma as a pentamer.
Each of the 5 subunits of this pentameric glycoprotein is made up of four chains: two identical 55 kDa “µ” heavy chains and two identical 25 kDa light chains that, when associated in the soluble pentameric form, weigh about 970 kDa.
Light chains bind only to a portion of heavy chains through the formation of disulfide bridges between cysteine residues.
When these molecules are enzymatically hydrolyzed, this reaction results in two fragments, one of them "homogeneous", known as the constant region or Fc, and the other known as the variable region or Fab2 (also called the hypervariable region), capable of binding to an antigen.
The amino acid sequence of the heavy chain of immunoglobulin M, especially that of the constant region, is what defines its identity, as well as that of the other isotypes of antibodies that have been defined in animals, which together make up the superfamily immunoglobulins.
The tertiary structure of the heavy and light chains of this antibody consists of β-folded sheets connected to each other through loops of varying length that can be stabilized by disulfide bridges.
In the pentameric form, each monomer of the IgM interacts with a polypeptide chain of union called J chain, of 15 kDa and that allows the formation of the structure formed by the 5 monomers.
Since each monomer has the ability to bind two identical antigenic molecules, an IgM pentamer can bind 10 antigens simultaneously.
Features
Immunoglobulin M participates in the initial response against bacterial antigens, so it is usually the first antibody secreted by activated B cells during the immune response.
Since its soluble structure is capable of binding to a large number of antigen molecules, it has the ability to aggregate or agglutinate antigenic particles belonging to cells such as red blood cells, bacteria, protozoa and others.
This antibody is very important for the early neutralization of bacterial toxins and is also effective in mediating the activity of the complement system, promoting the rapid "opsonization" of antigenic particles.
Graphic representation of immunoglobulin M bound to antigenic epitopes of invading bacteria (Source: SA1590 via Wikimedia Commons)
Its monomeric form is generally found attached to the plasma membrane of "naive" B lymphocytes, as is the case with immunoglobulin D, and it has been determined that a large part of the B cell repertoire of neonates corresponds to lymphocytes with IgM in their membrane..
It is also worth highlighting the fact that it is the first immunoglobulin produced by “naive” B cells in fetuses during pregnancy, after the first antigenic stimulations.
Although in low concentration, immunoglobulin M has been found in the secretions of mammalian animals, a fact that suggests that it also participates in the immunological protection of body mucosa.
High (significant) IgM values
A person is considered to have high immunoglobulin values when studies show values above the normal range.
High plasma immunoglobulin M values may be indicative of recent exposure to an antigen, as well as an early stage of viral hepatitis and other pathological conditions such as:
- mononucleosis, - rheumatoid arthritis, - Waldenstrom's macroglobulinemia, - nephrotic syndrome (kidney damage)
- development of infections caused by parasitic agents
Another reason why high levels of IgM can be obtained in serum is the existence of “Hyper IgM” syndromes (HIGM). Patients with this syndrome are more susceptible to suffering from recurrent infections and even different types of cancer, since it causes a drastic drop in IgG levels.
Low values (meaning)
The existence of some significant pathologies such as multiple myelomas, some types of leukemias and certain inherited immunological diseases has been correlated with low levels of immunoglobulin M in serum.
Patients with Wiskott-Aldrich X-linked deficiency syndrome may have low levels of IgM, however a small increase in the levels of the other four immunoglobulins can compensate for the condition.
Low levels of IgM can indicate more severe conditions such as an immunoglobulin deficiency, which can have serious health implications, especially during exposure to new antigens or during the course of certain diseases.
These deficiencies can have many causes, from errors in antigen recognition systems to defects in the production of antibodies by B lymphocytes.
Levels as low as 40 mg / dL have been reported for those patients with selective IgM deficiencies, which consist of a "rare" form of dysgammaglobulinemia.
Normal values
The normal range of plasma immunoglobulin M concentration is highly variable and depends, among many things, on age. According to the different age groups, this antibody is in a concentration of:
- 26-122 mg / dL between 0 and 5 months
- 32-132 mg / dL between 5 and 9 months
- 40-143 mg / dL between 9 and 15 months
- 46-152 mg / dL between 15 and 24 months
- 37-184 mg / dL between 2 and 4 years
- 27-224 mg / dL between 4 and 7 years
- 35-251 mg / dL between 7 and 10 years
- 41-255 mg / dL between 10 and 13 years old
- 45-244 mg / dL between 13 and 16 years old
- 49-201 mg / dL between 16 and 18 years old
- 37-286 mg / dL in adults over 18 years of age, although some texts indicate that the range is between 45 and 150 mg / dL, between 45 and 250 mg / dL or between 60 and 360 mg / dL
It is important to mention that these concentration values of IgM are more or less 10 times lower than those of other important immunoglobulins such as IgG, for example.
References
- Actor, JK (2019). Introductory Immunology, 2nd: Basic Concepts for Interdisciplinary Applications. Academic Press.
- Bengten, E., Wilson, M., Miller, N., Clem, LW, Pilström, L., & Warr, GW (2000). Immunoglobulin isotypes: structure, function, and genetics. In Origin and Evolution of the Vertebrate Immune System (pp. 189-219). Springer, Berlin, Heidelberg.
- Burrell, CJ, Howard, CR, & Murphy, FA (2016). Fenner and White's Medical Virology. Academic Press.
- Casali, P. (1998). IgM. Elsevier.
- Hu, F., Zhang, L., Zheng, J., Zhao, L., Huang, J., Shao, W.,… & Qiu, X. (2012). Spontaneous production of immunoglobulin M in human epithelial cancer cells. PloS one, 7 (12).
- Kruetzmann, S., Rosado, MM, Weber, H., Germing, U., Tournilhac, O., Peter, HH,… & Quinti, I. (2003). Human immunoglobulin M memory B cells controlling Streptococcus pneumoniae infections are generated in the spleen. The Journal of experimental medicine, 197 (7), 939-945.
- Petar, P., Dubois, D., Rabin, BS, & Shurin, MR (2005). Immunoglobulin Titers and Immunoglobulin Subtypes. In Measuring Immunity (pp. 158-171). Academic Press.
- Sullivan, KE, & Stiehm, ER (Eds.). (2014). Stiehm's immune deficiencies. Academic Press.