pre-B cell allelic exclusion

Definition

Target type: biologicalprocess

Expression of a single heavy chain allele during pre-B cell differentiation. [GOC:add, GOC:jal, ISBN:0781735149]

Pre-B cell allelic exclusion is a critical process in B cell development that ensures each B cell expresses only one functional immunoglobulin (Ig) heavy chain allele. This process is essential for maintaining the integrity of the immune system and preventing autoimmunity.

The process begins with the rearrangement of Ig heavy chain genes in pro-B cells. During this process, the variable (V), diversity (D), and joining (J) gene segments of the Ig heavy chain locus are randomly recombined, resulting in a unique Ig heavy chain protein.

If this rearrangement is successful, the pro-B cell expresses the newly generated Ig heavy chain protein on its surface, along with surrogate light chains, forming the pre-B cell receptor (pre-BCR). The pre-BCR signals through a complex signaling pathway that leads to several critical events, including:

* **Allelic exclusion:** The pre-BCR signal blocks further rearrangement of the other Ig heavy chain allele. This ensures that only one functional Ig heavy chain allele is expressed in each B cell.
* **Pre-B cell proliferation:** The pre-BCR signal triggers a wave of proliferation, allowing the B cell to expand and generate a clonal population.
* **Light chain gene rearrangement:** The pre-BCR signal promotes the initiation of Ig light chain gene rearrangement.

After the light chain genes are successfully rearranged, the B cell expresses a complete Ig molecule on its surface, forming the mature B cell receptor (BCR). The BCR can now bind to specific antigens and initiate an immune response.

Pre-B cell allelic exclusion is a tightly regulated process involving several molecular mechanisms, including:

* **Chromatin modifications:** The pre-BCR signal induces changes in chromatin structure that prevent further rearrangements of the second Ig heavy chain allele.
* **Transcription factors:** Several transcription factors are involved in regulating Ig gene expression and ensuring allelic exclusion, including Pax5, E2A, and Ikaros.
* **Signaling pathways:** The pre-BCR signal activates several signaling pathways, including the PI3K/Akt, Ras/MAPK, and NF-κB pathways, which contribute to the regulation of allelic exclusion.

Failure of allelic exclusion can lead to the production of B cells that express multiple Ig heavy chains. This can result in autoimmunity, as these cells may produce antibodies that target self-antigens. Therefore, pre-B cell allelic exclusion is essential for maintaining immune homeostasis and preventing autoimmune diseases.'
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Compounds (20)