- … the antibody in serum is a mixture of perhaps
- 100 million slightly different types of molecule…
- J. H. L. Playfair and B. M. Chain41(p38)
- Plasma cells can release up to 2000 antibody mole-
- cules per second …
- J. H. L. Playfair and B. M. Chain41(p43)
- You are the antibody.
- Smash Mouth
Immunoglobulins are the glycoproteins that constitute antibodies. They were first recognized by serum electrophoresis and, because they were localized to the electrophoretic gamma zone, were originally referred to as γ-globulins.42-47
The term immunoglobulin and terminology for immunoglobulin classes were put forth in the 1960s.48-53 The use of the abbreviation Ig (pronounced [eye-gee]54) in preference to γ was suggested to avoid confusion with the IgG heavy chain, γ55 (see the “Heavy Chains” section below). The class of immunoglobulin molecules most abundant in serum was named IgG, the G deriving from the electrophoretic gamma mobility. The M in IgM originates in an earlier designation as a macroglobulin.
The 5 classes of immunoglobulins, from most to least abundant, are as follows:
gamma electrophoretic mobility
from β2A-globulin, later α-immunoglobulin
“process of elimination”54(p66): B reserved for mice, C had no Greek equivalent
E-reactive antibody associated with erythema of allergy
Each can be found either on a cell surface (where it serves as an antigen receptor) or in tissue fluids such as blood (where it serves as a protective antibody).
Figure 7 shows schematically the basic structural unit of all immunoglobulin molecules, including many components defined herein. An immunoglobulin can be composed of 1 such unit (monomer) or more.
Enzyme cleavage and antibody engineering result in fragments of the immunoglobulin molecule with specific names. Expansion of these terms is not necessary:
Fab with part of hinge
2 linked Fab′ fragments
variable part of Fab
Each immunoglobulin monomer contains 2 heavy chains and 2 light chains, abbreviated as follows:
Each H chain and L chain in turn contains both constant and variable regions, abbreviated as follows:
Regions of the Ig molecule may be indicated as follows:
variable region of heavy chain
variable region of light chain
constant region of heavy chain
constant region of light chain
Immunoglobulins have 3 or 4 CH domains, depending on isotype, abbreviated as follows:
The type of heavy chain identifies the class (isotype) of immunoglobulin. Heavy chains are named with the Greek letter that corresponds to the class of immunoglobulin:
IgG and IgA subclasses and corresponding heavy chains are as follows:
CH domains may be specified according to isotype:
Cε2 Cμ4 Cα3 Cγ3
There are 2 types of light chain (named for initials of the discoverers’ surnames55):
Both types of light chain are associated with all 5 immunoglobulin classes; that is, an immunoglobulin molecule of any type might have κ or λ light chains (but not both types in the same molecule). In humans, there are 6 classes (isotypes) of λ chain:
λ1 λ2 λ3 λ4 λ5 λ6
CL and VL regions may be specified by light chain type, as follows:
The 3 specific hypervariable regions within the variable regions of an immunoglobulin H or L chain are known as complementarity-determining regions (CDRs) and are named as follows:
CDR1 CDR2 CDR3
Heavy- and light-chain CDRs are termed HCDR1, etc, and LCDR1, etc, respectively.
The 4 framework regions (relatively invariable regions between hypervariable regions) are designated as follows:
FR1 FR2 FR3 FR4
The following are examples of terms combining Ig and a single-letter prefix. It is best to expand these terms at first mention (especially those with the letters m or s, each of which has more than 1 meaning):
receptor for polymeric immunoglobulin
Other Immunoglobulin Components.
The secretory forms of IgM and IgA contain an additional polypeptide, the J chain (not to be confused with the joining or J segments of the immunoglobulin gene loci; see the “Immunoglobulin Genetics” section below).
Secreted IgA also contains a secretory component, SC.
These indicate the number of polypeptide chains that constitute an immunoglobulin molecule:
IgG monomer with 2 γ chains and 2 light chains
IgA monomer with 2 α chains and 2 light chains
IgA dimer with 4 α chains, 4 light chains, an SC, and a J chain
IgM pentamer with 10 μ chains and 10 light chains
IgM pentamer with 10 μ chains, 10 light chains, and a J chain
IgD monomer with 2 δ chains and 2 κ light chains
IgE monomer with 2 ε chains and 2 λ light chains
Fc Fragments and Fc Receptors.
Fc fragments may be specified by the heavy-chain class from which they arise57:
Receptors for the Fc portion of immunoglobulin molecules are named as follows (cell surface marker identities, if applicable, are shown in parentheses; see 15.8.2, CD Cell Markers):
FcγRIIIA or FcγRIIIa
FcγRIIIB or FcγRIIIb
(immunoglobulin-associated α; CD79a; this is not IgA or the α heavy chain)
(immunoglobulin-associated β; CD79b)
Serologic markers associated with some heavy and light chains are indicated with roman letters and a lowercase m:
A2m, A2m(1), A2m(2)58
Each immunoglobulin light chain gene is made up of a variable (V), joining (J), and constant (C) gene segment. Each immunoglobulin heavy chain is made up of V, J, C, and D (diversity) gene segments. These segments can be referred to as follows:
VH VL JH JL CH CL DH
or, more specifically, as in the following (subscript numbers refer to the class of Ig):
Vκ Vλ Jκ Cλ2 Cμ Cα2
Subgroups (various nonallelic forms) of V, D, J, and C gene segments are specified numerically (subscript numbers refer to the class of Ig, numbers set on the line refer to the subgroup), as in:
Vκ1 Vλ3 DH1 DH3 Cα25 Cλ11 Cλ2 Jκ2 JH1
A superscript plus sign may be used to indicate expression of a specific segment, eg, by a particular B lymphocyte (see 15.8.7, Lymphocytes):
The V, D, and J gene segments are brought together by DNA rearrangement. Descriptive terms for this process include the following:
V/J exon, segment, region, gene, recombination
in L-chain genes
V/D/J exon, segment, region, gene, recombination
in H-chain genes
L- and/or H-chain genes
VDJ, V/D/J, V-D-J, variable-diversity-joining
A leader segment (L), which codes for a leader (L) peptide, precedes each V segment. Note the following potential sources of confusion:
V, D, and J segments code for the variable (V) region of an immunoglobulin protein.
J segment does not refer to the J chain of the secretory forms of IgA and IgM (see the “Other Immunoglobulin Components” section above).
L (leader) gene segment and L (light) immunoglobulin chain are different entities. (Subscript L's, as in various terms in this section, typically refer to the light chain.)
Official Gene Terminology.
Official gene symbols for specific genes of the types discussed above are presented in the following table (see 15.6.2, Genetics, Human Gene Nomenclature). Follow author usage.
Official Gene Symbol
member of DH1 subgroup
member of VH1 subgroup
member of Vκ1 subgroup
member of Vλ1 subgroup