Question

Imagine an individual with a mutation such that they can not express Vpre-B protein. Answer the following:

When is VPre-B normally expressed (specific cell development stage and in what tissue)?

To what, specifically, does Vpre-B bind?

What are the outcomes of Vpre-B surface expression?

In the absence of Vpre-B expression, what is the most likely outcome for the patient? (what is the limitations of their immune system)?

Answer 1

1.  

• When VPre-B protien is normally expressed by precursor B cells in bone marrow and by a subset of normal germinal center B cells in secondary lymphoid organs.
• B cells are generated in the foetal liver. Subsequently in the adults, they are produced by differentiation of haematopoietic cells in the bone marrow
• B cell activation occurs in the secondary lymphoid organs (SLOs), such as the spleen and lymph nodes. After B cells mature in the bone marrow, they migrate through the blood to SLOs, which receive a constant supply of antigen through circulating lymph.The immune system is remarkable for its ability to respond to a great many antigens, including newly synthesized compounds which did not exist until recently. Successful synthesis of both H and L chains and their expression on the membrane are necessary for the development of B cells and mark the stages in that development.B cell development begins in the fetal liver and continues in the bone marrow throughout our lives.
• VpreB is normally expressed within the pro-B and pre-B cells in the bone marrow of λ5-deficient mice, the VpreB molecules alone do not associate with surrogate H chains to form pro-BCR

2.

mature B cells fail to bind antigen in the lymphoid follicles. pre-B cells bind ligand with their pre-B receptor and stop rearranging H chain genes

3.

The generation of B lymphocytes from committed progenitor cells is a complex process involving the transit of cells through several critical stages of development. Throughout their transit, developing B cells are subject to choices between survival, proliferation or death; fates that are dictated by combinations of intrinsic and extrinsic signals. Thus, failure to express certain signalling molecules on their surface at particular stages of development results in the cell failing to receive a viability and/or proliferative signal

4. Differences in th expression of surface membrane and cytoplasmic antigens are used to classify leukemias. Virtually all known single antigens as well as immunoglobulin and T-cell receptor gene rearrangements lack lineage specificity however, and the immunophenotypic classification is based on the pattern of reactivity to multipe antibodies . A panel of lineage- accociated antibodies is thus used to classify all into immunologic subtypes, which reflect the cell of origin and the stage of lymphoid defferentiation at which the malignant transformation occured.

An effective immune system must be able to discriminate such differences, distinguishing self from non-self and distinguishing harmless non-self from dangerous non-self.Despite the enhanced efficacy of memory cells and the recall immune response