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Delayed cellular maturation and decreased immunoglobulin kappa light chain production in immature B lymphocytes lacking B cell linker protein.

Xu S, Lam KP - J. Exp. Med. (2002)

Bottom Line: The mutant IgM(lo) and IgM(hi) cells are at an earlier developmental stage compared with the control IgM(hi) cells as indicated by their differential expression of CD43, B220, and major histocompatibility complex class II antigens and their timing of generation in culture.Furthermore, mutant IgM(lo) cells produce equivalent level of immunoglobulin (Ig) mu but less Ig kappa proteins than control and mutant IgM(hi) cells and this defect is attributed to a decrease in the amount of kappa transcripts being generated.Taken together, the data suggest a role for BLNK and perhaps BCR signaling, in the regulation of kappa light chain expression and continued immature B cell differentiation.

View Article: PubMed Central - PubMed

Affiliation: Institute of Molecular and Cell Biology, Singapore 117609, Singapore.

ABSTRACT
B cell linker (BLNK) protein is a component of the B cell receptor (BCR) signaling pathway and BLNK(-/-) mice have a block in B lymphopoiesis at the pro-B/pre-B cell stage. To study the effect of BLNK mutation at later stages of B cell development, we introduce an innocuous transgenic BCR into BLNK(-/-) mice and show that two populations of immature B cells distinguishable by their IgM(low (lo)) and IgM(high (hi)) phenotypes are found in the bone marrow of these mice in contrast to a single population of IgM(hi) cells found in control BCR-transgenic BLNK(+/+) mice. The mutant IgM(lo) and IgM(hi) cells are at an earlier developmental stage compared with the control IgM(hi) cells as indicated by their differential expression of CD43, B220, and major histocompatibility complex class II antigens and their timing of generation in culture. Thus, in the absence of BLNK the differentiation of immature B cells is delayed. Furthermore, mutant IgM(lo) cells produce equivalent level of immunoglobulin (Ig) mu but less Ig kappa proteins than control and mutant IgM(hi) cells and this defect is attributed to a decrease in the amount of kappa transcripts being generated. Finally, splenic B cells in BCR-transgenic BLNK(-/-) mice are predominantly of the transitional B cell phenotype and are rapidly lost from the peripheral B cell pool. Taken together, the data suggest a role for BLNK and perhaps BCR signaling, in the regulation of kappa light chain expression and continued immature B cell differentiation.

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Turnover of splenic B cells in TG1 BLNK−/− mice. Groups of five TG1 BLNK+/+ and TG1 BLNK−/− mice were continuously fed with BrdU in drinking water for a period of 1 wk and splenic B220+IgM+ cells were stained for their intracellular BrdU content. Statistical significance is determined by a paired two-tailed Student's t test.
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fig9: Turnover of splenic B cells in TG1 BLNK−/− mice. Groups of five TG1 BLNK+/+ and TG1 BLNK−/− mice were continuously fed with BrdU in drinking water for a period of 1 wk and splenic B220+IgM+ cells were stained for their intracellular BrdU content. Statistical significance is determined by a paired two-tailed Student's t test.

Mentions: As B cells in TG1 BLNK−/− mice are arrested at the transitional T1 cell stage, they are likely to be short-lived (27) and not selected into the long-lived mature B cell pool (29). Indeed, one would expect a higher rate of turnover of peripheral B cells in the mutant mice, and this might account for the loss of cells in these animals. To determine if this is the case, we examine the rate of turnover of the peripheral B cells in the mutant mice. TG1 BLNK+/+ and TG1 BLNK−/− mice were fed with BrdU in drinking water and the fraction of splenic B cells that had incorporated BrdU over a 1-wk period was determined. As shown in Fig. 9 , the fraction of IgM+ B cells that had incorporated BrdU in the mutant mice is approximately twice that of the wild-type mice, suggesting that there is a greater loss of peripheral B cells in the absence of BLNK.


Delayed cellular maturation and decreased immunoglobulin kappa light chain production in immature B lymphocytes lacking B cell linker protein.

Xu S, Lam KP - J. Exp. Med. (2002)

Turnover of splenic B cells in TG1 BLNK−/− mice. Groups of five TG1 BLNK+/+ and TG1 BLNK−/− mice were continuously fed with BrdU in drinking water for a period of 1 wk and splenic B220+IgM+ cells were stained for their intracellular BrdU content. Statistical significance is determined by a paired two-tailed Student's t test.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2193924&req=5

fig9: Turnover of splenic B cells in TG1 BLNK−/− mice. Groups of five TG1 BLNK+/+ and TG1 BLNK−/− mice were continuously fed with BrdU in drinking water for a period of 1 wk and splenic B220+IgM+ cells were stained for their intracellular BrdU content. Statistical significance is determined by a paired two-tailed Student's t test.
Mentions: As B cells in TG1 BLNK−/− mice are arrested at the transitional T1 cell stage, they are likely to be short-lived (27) and not selected into the long-lived mature B cell pool (29). Indeed, one would expect a higher rate of turnover of peripheral B cells in the mutant mice, and this might account for the loss of cells in these animals. To determine if this is the case, we examine the rate of turnover of the peripheral B cells in the mutant mice. TG1 BLNK+/+ and TG1 BLNK−/− mice were fed with BrdU in drinking water and the fraction of splenic B cells that had incorporated BrdU over a 1-wk period was determined. As shown in Fig. 9 , the fraction of IgM+ B cells that had incorporated BrdU in the mutant mice is approximately twice that of the wild-type mice, suggesting that there is a greater loss of peripheral B cells in the absence of BLNK.

Bottom Line: The mutant IgM(lo) and IgM(hi) cells are at an earlier developmental stage compared with the control IgM(hi) cells as indicated by their differential expression of CD43, B220, and major histocompatibility complex class II antigens and their timing of generation in culture.Furthermore, mutant IgM(lo) cells produce equivalent level of immunoglobulin (Ig) mu but less Ig kappa proteins than control and mutant IgM(hi) cells and this defect is attributed to a decrease in the amount of kappa transcripts being generated.Taken together, the data suggest a role for BLNK and perhaps BCR signaling, in the regulation of kappa light chain expression and continued immature B cell differentiation.

View Article: PubMed Central - PubMed

Affiliation: Institute of Molecular and Cell Biology, Singapore 117609, Singapore.

ABSTRACT
B cell linker (BLNK) protein is a component of the B cell receptor (BCR) signaling pathway and BLNK(-/-) mice have a block in B lymphopoiesis at the pro-B/pre-B cell stage. To study the effect of BLNK mutation at later stages of B cell development, we introduce an innocuous transgenic BCR into BLNK(-/-) mice and show that two populations of immature B cells distinguishable by their IgM(low (lo)) and IgM(high (hi)) phenotypes are found in the bone marrow of these mice in contrast to a single population of IgM(hi) cells found in control BCR-transgenic BLNK(+/+) mice. The mutant IgM(lo) and IgM(hi) cells are at an earlier developmental stage compared with the control IgM(hi) cells as indicated by their differential expression of CD43, B220, and major histocompatibility complex class II antigens and their timing of generation in culture. Thus, in the absence of BLNK the differentiation of immature B cells is delayed. Furthermore, mutant IgM(lo) cells produce equivalent level of immunoglobulin (Ig) mu but less Ig kappa proteins than control and mutant IgM(hi) cells and this defect is attributed to a decrease in the amount of kappa transcripts being generated. Finally, splenic B cells in BCR-transgenic BLNK(-/-) mice are predominantly of the transitional B cell phenotype and are rapidly lost from the peripheral B cell pool. Taken together, the data suggest a role for BLNK and perhaps BCR signaling, in the regulation of kappa light chain expression and continued immature B cell differentiation.

Show MeSH
Related in: MedlinePlus