on 22.7.04 with 0 comments

Human antibodies exhibit an enormous range (~108) of specificity’s. The genetic basis for this involves several factors:
VDJ recombination

1. the heavy chain of the immunoglobulin is made up of a variable (V), diversity (D), and junctional/joining (J) segment.

2. The gene possesses greater than 200 V, 20 D, and 6 J coding sequences.

3. During B cell development the sequences between the V, D, and J sequences are removed via recombination to provide for a single open reading frame.

4. Heavy chain recombination precedes light chain rearrangement.

5. The light chains can utilize either the kappa or lambda genes for generation of a functional Ig protein.

6. Light chain possesses V and J segments: No D

7. During B cell development, the sequence between the V segment (more than 100 coding sequences) and the J segment (1 or more J segments, depending on the light chain) is removed via recombination to provide for a single open reading frame.

B. Class switching

1. Only the heavy chain

2. The isotype is defined by those sequences (known as the constant region, i.e. codes for IgG, IgM etc.) that are invariable and downstream of the VDJ recombination.

3. Isotype switching utilizes recombination to remove such constant region sequences so as to allow the VDJ sequence to be placed upstream of different C regions.

C. Affinity maturation

1. After the B cells have been activated and class switched, a portion are found that migrate to the spleen and lymph nodes. Two things happen:

a) rapid proliferation, every 6-12 hours=1 division

b) B cells sustain somatic mutation at Ig chains.

2. Aim of this process is to create Ig with higher affinity for antigen

3. Those B cells that lose affinity for antigen are eliminated.

Category: Pathology Notes



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