Abstract
B cells play a pivotal role in adaptive immune system, since they maintain a delicate balance between recognition and clearance of foreign pathogens and tolerance to self. During maturation, B cells progress through a series of developmental stages defined by specific phenotypic surface markers and the rearrangement and expression of immunoglobulin (Ig) genes. To get insight into B cell proteome during the maturation pathway, we studied differential protein expression in eight human cell lines, which cover four distinctive developmental stages; early pre-B, pre-B, plasma cell and immature B cell upon anti-IgM stimulation. Our two-dimensional differential gel electrophoresis (2D-DIGE) and mass spectrometry based proteomic study indicates the involvement of large number of proteins with various functions. Notably, proteins related to cytoskeleton were relatively highly expressed in early pre-B and pre-B cells, whereas plasma cell proteome contained endoplasmic reticulum and Golgi system proteins. Our long time series analysis in anti-IgM stimulated Ramos B cells revealed the dynamic regulation of cytoskeleton organization, gene expression and metabolic pathways, among others. The findings are related to cellular processes in B cells and are discussed in relation to experimental information for the proteins and pathways they are involved in. Representative 2D-DIGE maps of different B cell maturation stages are available online at http://structure.bmc.lu.se/BcellProteome/.
Highlights
Bcells play a pivotal role in adaptive immune system, since they are needed to maintain a delicate balance between recognition and clearance of foreign pathogens and tolerance to self
Our time scale analysis suggests that those proteins known to be important in the very early stages upon B cell antigen receptor (BCR) stimulation are re-regulated in 24 hours
Our study revealed co-expression and -regulation of nearly 190 proteins related to the cellular processes and signalling pathways in the B cell differentiation pathway from early pre-B to terminally differentiated plasma cell stage
Summary
Bcells play a pivotal role in adaptive immune system, since they are needed to maintain a delicate balance between recognition and clearance of foreign pathogens and tolerance to self. During their maturation, B cells progress through a series of developmental stages defined by specific phenotypic surface markers and the rearrangement and expression of immunoglobulin (Ig) coding genes (for review see [1]). The maturation begins in bone marrow and foetal liver, and proceeds through ordered series of steps resulting in the release of immature B cells expressing surface IgM. Once activated, following engagement of B cell antigen receptor (BCR) with antigen, mature B cells move to germinal centres in the lymphoid tissue and, with help of other cells, differentiate into antibody-secreting plasma or memory B cells
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