The Ii antigen system is a

human blood group system The term human blood group systems is defined by the International Society of Blood Transfusion (ISBT) as systems in the human species where cell-surface antigens—in particular, those on blood cells—are "controlled at a single gene locus or by ...

based upon a gene on

chromosome 6 Chromosome 6 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 6 spans more than 170 million base pairs (the building material of DNA) and represents between 5.5 and 6% of the total ...

and consisting of the I antigen and the i antigen. The I antigen is normally present on the cell membrane of

red blood cells Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek language, Greek ''erythros'' for "red" and ''k ...

in all adults, while the i antigen is present in

fetuses A fetus or foetus (; plural fetuses, feti, foetuses, or foeti) is the unborn offspring that develops from an animal embryo. Following embryonic development the fetal stage of development takes place. In human prenatal development, fetal develo ...

and newborns.

I and i antigens

Adult red blood cells express I antigen abundantly. Developing fetuses and newborns express i antigen until around 13-20 months after birth, when I antigen starts to be expressed instead. Like ABH antigens, which make up the ABO blood group, I and i antigens are not restricted to the red blood cell membrane, but are found on most human cells and in body fluids such as

saliva Saliva (commonly referred to as spit) is an extracellular fluid produced and secreted by salivary glands in the mouth. In humans, saliva is around 99% water, plus electrolytes, mucus, white blood cells, epithelial cells (from which DNA can be ...

. The I and i antigens are

carbohydrate In organic chemistry, a carbohydrate () is a biomolecule consisting of carbon (C), hydrogen (H) and oxygen (O) atoms, usually with a hydrogen–oxygen atom ratio of 2:1 (as in water) and thus with the empirical formula (where ''m'' may or ma ...

structures composed of repeating units of ''N''-acetyllactosamine (LacNAc), and are located on the interior of structures carrying ABH and

Lewis Lewis may refer to: Names * Lewis (given name), including a list of people with the given name * Lewis (surname), including a list of people with the surname Music * Lewis (musician), Canadian singer * "Lewis (Mistreated)", a song by Radiohead ...

antigens. LacNAc repeats are made by the enzymes B3GNT1 and

B4GALT1 Beta-1,4-galactosyltransferase 1 is an enzyme that in humans is encoded by the ''B4GALT1'' gene. This gene is one of seven beta-1,4-galactosyltransferase (beta4GalT) genes. They encode type II membrane-bound glycoproteins that appear to have excl ...

. The i antigen is made of linear repeats, while the structure of the I antigen is branched. Unlike most other blood groups, the two antigens are not encoded by different

allele An allele (, ; ; modern formation from Greek ἄλλος ''állos'', "other") is a variation of the same sequence of nucleotides at the same place on a long DNA molecule, as described in leading textbooks on genetics and evolution. ::"The chro ...

s; rather, I-branching enzyme converts i antigen to I antigen by adding branches. The gene encoding I-branching enzyme is located on chromosome 6.

Clinical significance

The function of I and i antigens are unknown but may be related to

hematopoiesis Haematopoiesis (, from Greek , 'blood' and 'to make'; also hematopoiesis in American English; sometimes also h(a)emopoiesis) is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. ...

, the production of blood. The rapid conversion from i to I antigens after birth suggests that I antigen plays an important role in adult red blood cells. The presence of the linear i antigen in fetuses, rather than the branched I antigen, may have developed as an

evolutionary Evolution is change in the heredity, heritable Phenotypic trait, characteristics of biological populations over successive generations. These characteristics are the Gene expression, expressions of genes, which are passed on from parent to ...

mechanism to prevent ABO hemolytic disease of the fetus and newborn. Enhanced expression of i antigen is associated with conditions involving stress hematopoiesis such as

leukemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ' ...

and

sickle cell disease Sickle cell disease (SCD) is a group of blood disorders typically inherited from a person's parents. The most common type is known as sickle cell anaemia. It results in an abnormality in the oxygen-carrying protein haemoglobin found in red blo ...

. Transient

autoantibodies An autoantibody is an antibody (a type of protein) produced by the immune system that is directed against one or more of the individual's own proteins. Many autoimmune diseases (notably lupus erythematosus) are associated with such antibodies. Pr ...

against I antigen are common, especially after infection by ''

Mycoplasma pneumoniae ''Mycoplasma pneumoniae'' is a very small bacterium in the class Mollicutes. It is a human pathogen that causes the disease mycoplasma pneumonia, a form of atypical bacterial pneumonia related to cold agglutinin disease. ''M. pneumoniae'' is char ...

'', and are rarely significant except in

cold agglutinin disease Cold agglutinin disease (CAD) is a rare autoimmune disease characterized by the presence of high concentrations of circulating cold sensitive antibodies, usually IgM and autoantibodies that are also active at temperatures below , directed again ...

. Transient antibodies against i antigen are common after

infectious mononucleosis Infectious mononucleosis (IM, mono), also known as glandular fever, is an infection usually caused by the Epstein–Barr virus (EBV). Most people are infected by the virus as children, when the disease produces few or no symptoms. In young adult ...

and are also not clinically significant. Antibodies which recognize both I and i antigens are termed anti-j antibodies.

Cold agglutinin disease

The autoantibodies involved in cold agglutinin disease are usually against I antigen. The antibodies are usually

IgM Immunoglobulin M (IgM) is one of several isotypes of antibody (also known as immunoglobulin) that are produced by vertebrates. IgM is the largest antibody, and it is the first antibody to appear in the response to initial exposure to an antig ...

(

kappa Kappa (uppercase Κ, lowercase κ or cursive ; el, κάππα, ''káppa'') is the 10th letter of the Greek alphabet, representing the voiceless velar plosive sound in Ancient and Modern Greek. In the system of Greek numerals, has a value o ...

subtype), unlike transient autoantibodies which are generally

IgG Immunoglobulin G (Ig G) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are created and released by plasma B cells. Each IgG ...

. Cold-reactive IgM antibodies (

cold agglutinins Cold sensitive antibodies (CSA) are antibodies sensitive to cold temperature. Some cold sensitive antibodies are pathological and can lead to blood disorder. These pathological cold sensitive antibodies include cold agglutinins, Donath–Landstei ...

) bind to I antigen on red blood cells, and unlike IgG, are able to cause

agglutination In linguistics, agglutination is a morphological process in which words are formed by stringing together morphemes, each of which corresponds to a single syntactic feature. Languages that use agglutination widely are called agglutinative lang ...

of red blood cells and activate

complement A complement is something that completes something else. Complement may refer specifically to: The arts * Complement (music), an interval that, when added to another, spans an octave ** Aggregate complementation, the separation of pitch-class ...

to cause

hemolysis Hemolysis or haemolysis (), also known by several other names, is the rupturing (lysis) of red blood cells (erythrocytes) and the release of their contents (cytoplasm) into surrounding fluid (e.g. blood plasma). Hemolysis may occur in vivo o ...

, leading to

anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, th ...

Adult i phenotype

Rarely, individuals have the i antigen on their red blood cells into adulthood, known as the adult i phenotype. This is due to the presence of a

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...

in the GCNT2 gene which encodes the I-branching enzyme. These individuals have

alloantibodies Alloimmunity (sometimes called isoimmunity) is an immune response to nonself antigens from members of the same species, which are called alloantigens or isoantigens. Two major types of alloantigens are blood group antigens and histocompatibility an ...

against the I antigen, though these are typically cold agglutinins and are unlikely to cause

transfusion reactions Blood transfusion is the process of transferring blood products into a person's circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used whole blood, but mo ...

. The adult i phenotype is associated with

congenital cataract Congenital cataracts refers to a lens opacity which is present at birth. Congenital cataracts cover a broad spectrum of severity: whereas some lens opacities do not progress and are visually insignificant, others can produce profound visual impa ...

s, most markedly in Japanese and Taiwanese people and least markedly in Caucasian people. Cataracts occur when i antigen rather than I antigen is present on the

epithelium Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellul ...

of the

lens A lens is a transmissive optical device which focuses or disperses a light beam by means of refraction. A simple lens consists of a single piece of transparent material, while a compound lens consists of several simple lenses (''elements''), ...

, due to a mutation in the form of the I-branching enzyme which is expressed in lens epithelium, IGNTB. The adult i phenotype is inherited in a

recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

manner.

History

The I antigen was first described in 1956 and the i antigen was discovered in 1960. I and i were the first discovered antigens which change significantly during

human development Human development may refer to: * Development of the human body * Developmental psychology * Human development (economics) * Human Development Index, an index used to rank countries by level of human development * Human evolution, the prehistoric ...

. The letter I was chosen to reflect the "individuality" of a person studied who lacked the I antigen.

Other species

A similar blood group system with a developmental change resembling the Ii system (with human neonatal cells expressing i antigen and adult cells expressing I antigen) has been observed in most

primates Primates are a diverse order of mammals. They are divided into the strepsirrhines, which include the lemurs, galagos, and lorisids, and the haplorhines, which include the tarsiers and the simians (monkeys and apes, the latter including huma ...

, including

chimpanzees The chimpanzee (''Pan troglodytes''), also known as simply the chimp, is a species of great ape native to the forest and savannah of tropical Africa. It has four confirmed subspecies and a fifth proposed subspecies. When its close relative the ...

and

monkeys Monkey is a common name that may refer to most mammals of the infraorder Simiiformes, also known as the simians. Traditionally, all animals in the group now known as simians are counted as monkeys except the apes, which constitutes an incomple ...

. This is not seen in non-primates:

cats The cat (''Felis catus'') is a domestic species of small carnivorous mammal. It is the only domesticated species in the family Felidae and is commonly referred to as the domestic cat or house cat to distinguish it from the wild members of t ...

dogs The dog (''Canis familiaris'' or ''Canis lupus familiaris'') is a domesticated descendant of the wolf. Also called the domestic dog, it is derived from the extinct Pleistocene wolf, and the modern wolf is the dog's nearest living relative. Do ...

, or

guinea pigs The guinea pig or domestic guinea pig (''Cavia porcellus''), also known as the cavy or domestic cavy (), is a species of rodent belonging to the genus ''Cavia'' in the family Caviidae. Breeders tend to use the word ''cavy'' to describe the ani ...

References

External links

Ii
at

BGMUT The BGMUT (Blood Group antigen gene MUTation) Database documents allelic variations in the genes encoding for human blood group systems. It was set up in 1999 through an initiative of the Human Genome Variation Society ( HGVS). Since 2006, it has ...

Blood Group Antigen Gene Mutation Database at

NCBI The National Center for Biotechnology Information (NCBI) is part of the United States National Library of Medicine (NLM), a branch of the National Institutes of Health (NIH). It is approved and funded by the government of the United States. The ...

NIH The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...

{{transfusion medicine Blood antigen systems Transfusion medicine Genes on human chromosome 6