2.1.4 Isotypes and subisotypes of Igs

There are five isotypes (classes) of Igs that are structurally and functionally distinct, IgM, IgD, IgG, IgA, and IgE. The difference between the classes of Igs lies in the constant portion of the H chains: mu (μ) determines the IgM class, gamma (γ) determines the IgG class, alpha (α) determines the IgA class, delta (δ) determines the IgD class, and epsilon (ε) determines the IgE class. So the DNA encoding the constant part of an H chain contains several constant sequences. Thus, there are four subclasses of IgG in both humans (IgG1, IgG2, IgG3, IgG4) and mice (IgG1, IgG2a, IgG2b, and IgG3) and two subclasses of IgA (IgA1 and IgA2) in humans, which are unequally distributed in the body fluids [22].



Key Point 1jMain features of human Ig classes and subclasses mIg sIg Properties

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Introductory Chapter: B-Cells

MW Secretory tetramer IgA1 or IgA2: 600

Structure Monomers, dimers (more common),

Serum concentration Total IgA : 1–4 mg/mL (IgA1: 3 mg/ mL; IgA2 : 0.5 mg/mL)

160 kDa

rare) H chain typejMW α1j55 kDa, α2j55 kDa

In vivo serum half life IgA1: 6 days; IgA2: 6 days Secretion Milk and secretions (tears, saliva,

13–15%

secretions)

10%

Distribution Intravascular and secretions

Function Protects mucous membranes

None

0.2%

13%

Function Somewhat unknown; while research

have demonstrated its role in promoting immune defense related to inflammation and tissue damage by

Distribution Lymphocyte surface

Crosses placenta None

Valency 2, 4, 6 or 8

Relative serum abundance to total immunoglobulin

Relative serum abundance to total

Carbohydrate content by weight (glycosylation)

Crosses placenta None

Molecular formula δ2κ<sup>2</sup> or δ2λ<sup>2</sup> Subclasses None MW 180 kDa Valency 2 Structure Monomers H chain typejMW δj62–70 kDa Serum concentration 0–0.4 mg/mL In vivo serum half life 3 days

Classical complement pathway activation

Relative serum abundance to total immunoglobulin

Carbohydrate content by weight (glycosylation)

7

IgA

kDa; serum monomer IgA1 or IgA2:

and trimers and tetramers (both are

mucous, sweat, colostrum, and secretions from the genitourinary tract, gastrointestinal tract, prostate, and respiratory mucosa)

IgA1; 85%, IgA2: 15% (higher in

### Introductory Chapter: B-Cells DOI: http://dx.doi.org/10.5772/intechopen.90636

Key Point 1jMain features of human Ig classes and subclasses mIg sIg Properties

Normal and Malignant B-cell

6

Serum concentration 0.5–2 mg/mL In vivo serum half life 5 days

6–10%

12%

Function Primary antibody response

+++

Subclasses Yes (IgG1, IgG2, IgG3, IgG4) MW IgG1; 150 kDa, IgG2; 150 kDa, IgG3; 170 kDa, IgG4; 150 kDa

H chain typejMW γ1j50 kDa, γ2j50 kDa, γ3j60 kDa, γ4j50 kDa Serum concentration Total IgG: 10–16 mg/mL (IgG1: 9 mg/

75–80%

3%

Distribution Intra- and extravascular

Crosses placenta IgG1: +; IgG2: +/�; IgG3: +; IgG4: + Function Secondary antibody response

Subclasses Yes (IgA1, IgA2) [in humans, serum

secretory piece.]

none

Molecular formula (α2κ2)n or (α2λ2)n

IgG4: 0.5 mg/mL) In vivo serum half life IgG1: 23 days; IgG2: 23 days; IgG3: 8 days; IgG4: 23 days

mL; IgG2: 3 mg/mL; IgG3: 1 mg/mL;

IgG1: +; IgG2: +/�; IgG3: ++; IgG4:

IgA are mostly monomers, but a small amount of them is found in polymeric forms (pIgA), usually dimers, linked by disulfide bonds and by an additional, cysteine-rich polypeptide termed J chain (16 kDa). Serum monomeric IgA can also be found in most secretions. Mucosal secretory IgAs are mostly seen as a dimer with a

Distribution Mainly intravascular

Crosses placenta None

Molecular formula γ2κ<sup>2</sup> or γ2λ<sup>2</sup>

Classical complement pathway activation

Valency 2 Structure Monomer

Relative serum abundance to total immunoglobulin

Carbohydrate content by weight (glycosylation)

Classical complement pathway activation

Relative serum abundance to total immunoglobulin

Carbohydrate content by weight (glycosylation)



2.4 Transmembrane vs. secreted B-cell receptor

DOI: http://dx.doi.org/10.5772/intechopen.90636

Introductory Chapter: B-Cells

differentiation; mIg, membrane-bound immunoglobulin.

Figure 3.

Figure 4.

9

The only structural difference between transmembrane and secreted B-cell receptors (soluble immunoglobulins, sIgs) is that the C-terminal region of the heavy

BCR complex structure. The BCR complex is composed of a mIg non-covalently bonded to a transmembrane disulfide-linked heterodimer phosphoprotein composed of CD79a (Igα)/CD79b (Igβ). CD, cluster of

Structural difference between the C-terminus of the H chain constant region of mIgM and sIgM. mIgM and sIgM differ simply by the COOH ends of the μ chain and therefore by mRNAs that differ at their 3<sup>0</sup> ends. Membrane-bound IgM (membrane μ) is slightly larger than that of secreted IgM (secreted μ) [27]. The numbers indicate the position of amino acids. N-CHO represents the position of glycosylation of asparagine (N, Asn) (N-glycosylation site). mIgM, membrane immunoglobulin M; sIgM, secreted immunoglobulin M.

### 2.2 Transmembrane B-cell receptor

B-cells are defined by the presence of membrane-bound Igs (mIg) that act as specific receptors for the appropriate antigen in mature B-cell but, also as an excellent marker of the B-cell line. The mIg constitutes, with other glycoprotein chains, the B-cell antigen receptor complex (BCR). These correspond to non-covalently associated transmembrane disulfide-linked heterodimer phosphoprotein Igα/Igβ (CD79a and CD79b), which are encoded by mb-1 and B29 genes, and are structurally similar to CD3γ, δ, and ε chains on T-cells and therefore involved in signal transduction of B-cell [23] (Figure 3). The intracytosolic portion size of the heterodimer allows it to initiate signal transduction, following the binding of the specific antigen to the mIg.

### 2.3 Mobility of mIgs, capping, and antigenic modulation

Igs are very mobile on the surface of B-cells. In addition, various specific ligands cause what is called capping, i.e., a rapid redistribution of complexes on the surface of the cell, followed by internalization of the complexes or their release into the surrounding environment. This transient disappearance of the mIg receptor via its binding to specific ligands, like anti-immunoglobulin antibodies or antigens, is called antigenic modulation, which constitutes the initial signal for B-cell activation. The modulated membrane receptor may also be synthesized by the cell and returned to the surface when the B-cell is metabolically active [24, 25].
