Unformatted text preview: B-cell Development Figure 4-1 Figure 4-2 Figure 4-3 ProB cells Early Stages of B-Cell Differentiation PreBcells Earliest distinguishable cell in the Bcell lineage DJ rearrangement has occurred No immunoglobulin product is produced Late ProB cells VDJ rearrangement V gene segment rearranges to join the DJ segments Early Stages of B-Cell Differentiation (cont.) heavy chain is produced The chain is expressed as a transmembrane molecule in association with the products of two nonrearranging genes 5 and VpreB (together they serve as surrogate light chains) This complex is associated with two additional transmembrane molecules Ig and Ig which are linked by disulfide bonds The entire complex ( , surrogate light chains Ig and Ig ) is referred to as the PreBcell receptor. Ig and Ig are signal transduction molecules. During Bcell differentiation, cells that do not express the preBCR die by apoptosis Cells expressing the preBCR undergo further differentiation, called positive selection, mediated by signal transmitted by the preBCR Early Stages of B-Cell Differentiation (cont.) Early Stages of B-Cell Differentiation (cont.) As a result of these signals the cell is induced to proliferate, surrogate light chain synthesis is shut down, light chain gene rearrangement begins and further heavy chain rearrangement stops. Figure 4-4 Early Stages of B-Cell Differentiation (cont.) Immature Bcells Light chains pair with chains to form monomeric IgM, which is inserted into the cell membrane The Cells bear only monomeric IgM as their antigen specific BCR At this stage of development, cells with the potential to react with self antigens are prevented from responding by deletion or anergy Early Stages of B-Cell Differentiation (cont.) This process is called negative selection. Receptor editing can also occur at this stage of differentiation Receptor editing involves secondary rearrangement using unrearranged V, D, or J gene segments. Receptor editing can occur in heavy or light chains. Figure 4-13 Figure 4-8 Late Stages of B-Cell Differentiation Mature BCells Mature Bcell has both IgM and IgD on its surface as Bcell antigen receptors. The antigen binding sites of IgM and IgD are identical. IgM and IgD are produced by alternate splicing. Signals which drive differentiation to the mature Bcell stage are unknown. Figure 4-3 Productive and Nonproductive Rearrangements Figure 4-7 Figure 4-9 Figure 4-10 B1 and B2 cells Figure 4-12 Figure 4-14 Figure 4-19 Figure 4-20 Figure 4-21 Figure 4-22 ...
View Full Document
This note was uploaded on 04/05/2008 for the course HSCI 3540 taught by Professor Gallagher during the Spring '06 term at East Tennessee State University.
- Spring '06