The PreBCell Receptor Is Essential for BCell Development

As we saw in Chapter 10, during one stage in T-cell development, the p chain of the T-cell receptor associates with preTa to form the pre-T-cell receptor (see Figure 10-1). A parallel situation occurs during B-cell development. In the pre-B cell, the membrane ^ chain is associated with the surrogate light chain, a complex consisting of two proteins: a V-like sequence called Vpre-B and a C-like sequence called

Pro-B cell

Pre-B cell

Immature B cell

Pro-B cell

Pre-B cell

Immature B cell

Prebcell Receptor

Stops VH' * DhJh (allelic exclusion) ?

Activation Death

Stops VH' * DhJh (allelic exclusion) ?

Crosslinking by antigen

Activation Death

Induces VK

FIGURE 11-4

Schematic diagram of sequential expression of membrane immunoglobulin and surrogate light chain at different stages of B-cell differentiation in the bone marrow. The pre-B-cell receptor contains a surrogate light chain consisting of a Vpre-B polypeptide and a \5 polypeptide, which are noncovalently associated. The immature B cell no longer expresses the surrogate light chain and instead expresses the k or \ light chain together with the ^ heavy chain.

Â.5, which associate noncovalently to form a light-chain-like structure.

The membrane-bound complex of ^ heavy chain and surrogate light chain appears on the pre-B cell associated with the Ig-a/Ig-p heterodimer to form the pre-B-cell receptor (Figure 11-4). Only pre-B cells that are able to express membrane-bound ^ heavy chains in association with surrogate light chains are able to proceed along the maturation pathway.

There is speculation that the pre-B-cell receptor recognizes a not-yet-identified ligand on the stromal-cell membrane, thereby transmitting a signal to the pre-B cell that prevents VH to DhJh rearrangement of the other heavy-chain allele, thus leading to allelic exclusion. Following the establishment of an effective pre-B-cell receptor, each pre-B cell undergoes multiple cell divisions, producing 32 to 64 descendants. Each of these progeny pre-B cells may then rearrange different light-chain gene segments, thereby increasing the overall diversity of the antibody repertoire.

The critical role of the pre-B-cell receptor was demonstrated with knockout mice in which the gene encoding the \5 protein of the receptor was disrupted. B-cell development in these mice was shown to be blocked at the pre-B stage, which suggests that a signal generated through the receptor is necessary for pre-B cells to proceed to the immature B-cell stage.

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Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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