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:

Class	Origin of Name⁴⁸^,⁵⁴
IgG	gamma electrophoretic mobility
IgA	from β_2A-globulin, later α-immunoglobulin
IgM	macroglobulin
IgD	“process of elimination”⁵⁴^(p66): B reserved for mice, C had no Greek equivalent
IgE	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.

Figure 7. Basic structural unit of immunoglobulin molecules. Adapted from Haynes and Fauci by permission of The McGraw-Hill Companies.56

Figure 7. Basic structural unit of immunoglobulin molecules. Adapted from Haynes and Fauci by permission of The McGraw-Hill Companies.⁵⁶

Enzyme cleavage and antibody engineering result in fragments of the immunoglobulin molecule with specific names. Expansion of these terms is not necessary:

Fab	antigen-binding fragment
Fab′	Fab with part of hinge
F(ab′)₂	2 linked Fab′ fragments
Fabc
Fb
Fc	crystallizable fragment
F′c
pFc′
Fd
Fv	variable part of Fab
scFv	single-chain Fv

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:

V_H	variable region of heavy chain
V_L	variable region of light chain
C_H	constant region of heavy chain
C_L	constant region of light chain

Immunoglobulins have 3 or 4 C_H domains, depending on isotype, abbreviated as follows:

C_H1

C_H2

C_H3

C_H4

Heavy Chains.

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:

Heavy-Chain Name	Immunoglobulin Class
γ	IgG
α	IgA
μ	IgM
δ	IgD
ε	IgE

IgG and IgA subclasses and corresponding heavy chains are as follows:

Heavy-Chain Name	Immunoglobulin Subclass
γ1	IgG1
γ2	IgG2
γ3	IgG3
γ4	IgG4
α1	IgA1
α2	IgA2

C_H domains may be specified according to isotype:

C_ε2 C_μ4 C_α3 C_γ3

Light Chains.

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

C_L and V_L regions may be specified by light chain type, as follows:

C_κ	C_λ
V_κ	V_λ

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

Ig Prefixes.

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):

mIgM	monomeric IgM
mIgM	membrane-bound IgM
pIg	polymeric immunoglobulin
pIgA	polymerized IgA
pIgR	receptor for polymeric immunoglobulin
sIg	surface immunoglobulin
sIgM	surface IgM
sIgA	secretory IgA

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.

Molecular Formulas.

These indicate the number of polypeptide chains that constitute an immunoglobulin molecule:

γ₂L₂	IgG monomer with 2 γ chains and 2 light chains
α₂L₂	IgA monomer with 2 α chains and 2 light chains
(α₂L₂)₂SCJ	IgA dimer with 4 α chains, 4 light chains, an SC, and a J chain
(μ₂L₂)₅	IgM pentamer with 10 μ chains and 10 light chains
(μ₂L₂)₅J	IgM pentamer with 10 μ chains, 10 light chains, and a J chain
δ₂κ₂	IgD monomer with 2 δ chains and 2 κ light chains
ε₂λ₂	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:

Fcγ1	Fcγ2	Fcγ3	Fcγ4
Fcα1	Fcα2
Fcμ
Fcδ
Fcε

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):

IgG receptors:
FcγRI	(CD64)
FcγRII	(CD32)
FcγRIIIA or FcγRIIIa	(CD16a)
FcγRIIIB or FcγRIIIb	(CD16b)

IgA receptor:
FcαR	(CD89)

IgM receptor:
FcμR

IgE receptors:
FcεRI
FcεRII	(CD23)

The 2 transmembrane accessory proteins associated with surface immunoglobulins on some immune cells should not be confused with terms for immunoglobulin classes or heavy chains:

Igα	(immunoglobulin-associated α; CD79a; this is not IgA or the α heavy chain)
Igβ	(immunoglobulin-associated β; CD79b)

Serologic markers associated with some heavy and light chains are indicated with roman letters and a lowercase m:

Marker	Associated Chain
G1m	γ1
G2m	γ2
G3m	γ3
A2m, A2m(1), A2m(2)⁵⁸	α2
Em	ε
Km	κ

Immunoglobulin Genetics.

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:

V_H V_L J_H J_L C_H C_L D_H

or, more specifically, as in the following (subscript numbers refer to the class of Ig):

V_κ V_λ J_κ C_λ2 C_μ C_α2

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:

V_κ1 V_λ3 D_H1 D_H3 C_α25 C_λ11 C_λ2 J_κ2 J_H1

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):

V_κ3⁺

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
V/(D)/J	L- and/or H-chain genes
VDJ, V/D/J, V-D-J, variable-diversity-joining	alternative terms

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	Immunogenetic Term
IGHA1	C_α1
IGHD	C_δ
IGHD1-1	member of D_H1 subgroup
IGHE	C_ε
IGHG1	C_γ1
IGHJ1	J_H1
IGHV@	V_H
IGHV1-2	member of V_H1 subgroup
IGKC	C_κ
IGKJ@	J_κ
IGKJ2	J_κ2
IGKV@	V_κ
IGKV1-5	member of V_κ1 subgroup
IGLC@	C_λ
IGLC1	C_λ1
IGLJ@	J_λ
IGLJ1	J_λ1
IGLV@	V_λ
IGLV1-36	member of V_λ1 subgroup

Alleles.

Alleles are indicated with an asterisk and number following the gene name:

IGHA1*01

IGHD*02

IGHD1-7*01

IGHE*03

IGHG3*04

IGHM*03

IGLJ1*01

IGLV2-11*01

For more detailed molecular information about immunoglobulin genetics, consult the International ImMunoGeneTics database (http://imgt.cines.fr).⁵⁹

Oxford University Press

PRINTED FROM AMA MANUAL OF STYLE ONLINE (www.amamanualofstyle.com). © American Medical Association, 2009. All Rights Reserved. Under the terms of the license agreement, an individual user may print out a PDF of a single chapter of a title in AMA Manual of Style Online for personal use (for details see Privacy Policy). Subscriber: null; date: 19 May 2013

Log out

Recently viewed (1)

AMA Manual of Style Committee

Immunoglobulins

Harriet S. Meyer

15.8.6 Immunoglobulins