Close Enough to Be B-Cell Receptors
IgM and IgD are the only antibody isotypes that can be expressed as both membrane-bound B cell receptors (BCRs) and secreted antibodies because of the unique genomic organization and close proximity of the constant mu (Cμ) and constant delta (Cδ) exons in the immunoglobulin heavy chain locus.
The immunoglobulin heavy chain locus contains multiple constant region gene segments arranged in the following order: Cμ, Cδ, Cγ3, Cγ1, Cα1, Cγ2, Cγ4, Cε, Cα2. During B cell development, the rearranged VDJ segment is joined to the Cμ exon first, producing an IgM molecule that can be expressed as either a membrane-bound IgM BCR or a secreted IgM antibody.
The Cδ exon is located immediately downstream of Cμ. Through alternative splicing, the same rearranged VDJ can be joined to Cδ instead of Cμ, allowing expression of a membrane-bound IgD BCR in naive B cells. This co-expression of IgM and IgD BCRs is important for augmenting antigen recognition capacity.
Too Far Away…
In contrast, the other antibody isotypes (IgG, IgA, IgE) are encoded by constant region genes located much further downstream in the locus. For class switching to occur to these other isotypes, the entire intervening stretch of DNA between the rearranged VDJ and the respective downstream C region must be deleted.
This deletion event, mediated by activation-induced cytidine deaminase (AID), only happens in activated B cells after antigen encounter. As a result, naive B cells can only express IgM and IgD BCRs due to the close genomic proximity of Cμ and Cδ. The other isotypes are exclusively expressed as secreted antibodies after class switching in activated B cells.
So in summary, the genomic organization allowing both BCR and secreted antibody expression of just IgM and IgD reflects their crucial roles in the initial antigen recognition by naive B cells versus the roles of the other isotypes in later stages of the antibody response.
Next Topic:
Source: Claude 3 Sonnet response prompted and edited by Joel Graff.
- Immunology (Table of Contents for Entire Course – FREE!)
- Other Content for Unit 4: Development of T Cells and B Cells
Life and Biology 