CD22 regulates early B cell development in BOB.1/OBF.1-deficient mice
Апстракт
BOB.1/OBF1 (also called OCA-B), a B lymphocyte-specific transcriptional coactivator, is recruited to octamer-containing promoters by interacting with the Oct-1 or Oct-2 proteins. BOB.1/OBF.1-deficient mice show impaired secondary immunoglobulin isotype secretion and complete absence of germinal centers. Furthermore, numbers of splenic B cells are reduced due to a developmental block at the transitional B cell stage in the bone marrow. We found that surface expression of CD22 is selectively increased on B lineage cells in the bone marrow of BOB.1/OBF.1-deficient mice. CD22 is known as a negative regulator of B cell receptor signaling. We therefore investigated whether defects in B cell development in the BOB.1/OBF1-deficient mice might be due to CD22 up-regulation. Mice were generated lacking both genes. In BOB.1/OBF.1 xCD22 double-deficient mice, numbers of transitional B cells in the bone marrow were normal. Consequently, double-deficient mice also had normal B to T cell ratios in the... spleen. We show that BOB.1/OBF.1(-/-) B cells were incapable to induce BCR-triggered Ca2+ mobilization. This Ca2+-signalling defect was restored in BOBA/ OBF1 xCD22 double-deficient B cells. Nevertheless, double-deficient animals were unable to mount humoral immune responses and to form germinal centers. Finally, we demonstrate that CD22(-/-) splenic B cells proliferate independently of BOB.1/OBF1 upon stimulation with LPS. These studies suggest that the B cell differentiation defect observed in BOB.1/OBF.1(-/-) mice is BCR-signal dependent. However, the impairment in germinal center formation is caused by a different mechanism.
Кључне речи:
B lymphocyte / cell surface molecule / transcription factor / cellular differentiation / signal transductionИзвор:
European Journal of Immunology, 2002, 32, 9, 2481-2489Издавач:
- Wiley-V C H Verlag Gmbh, Weinheim
DOI: 10.1002/1521-4141(200209)32:9_2481::AID-IMMU2481>3.0.CO;2-C
ISSN: 0014-2980
PubMed: 12207332
WoS: 000178144900011
Scopus: 2-s2.0-0036737191
Институција/група
rFASPERTY - JOUR AU - Samardžić, T. AU - Gerlach, J AU - Muller, K AU - Marinković, Dragan AU - Hess, J AU - Nitschke, L. AU - Wirth, Thomas PY - 2002 UR - http://rfasper.fasper.bg.ac.rs/handle/123456789/29 AB - BOB.1/OBF1 (also called OCA-B), a B lymphocyte-specific transcriptional coactivator, is recruited to octamer-containing promoters by interacting with the Oct-1 or Oct-2 proteins. BOB.1/OBF.1-deficient mice show impaired secondary immunoglobulin isotype secretion and complete absence of germinal centers. Furthermore, numbers of splenic B cells are reduced due to a developmental block at the transitional B cell stage in the bone marrow. We found that surface expression of CD22 is selectively increased on B lineage cells in the bone marrow of BOB.1/OBF.1-deficient mice. CD22 is known as a negative regulator of B cell receptor signaling. We therefore investigated whether defects in B cell development in the BOB.1/OBF1-deficient mice might be due to CD22 up-regulation. Mice were generated lacking both genes. In BOB.1/OBF.1 xCD22 double-deficient mice, numbers of transitional B cells in the bone marrow were normal. Consequently, double-deficient mice also had normal B to T cell ratios in the spleen. We show that BOB.1/OBF.1(-/-) B cells were incapable to induce BCR-triggered Ca2+ mobilization. This Ca2+-signalling defect was restored in BOBA/ OBF1 xCD22 double-deficient B cells. Nevertheless, double-deficient animals were unable to mount humoral immune responses and to form germinal centers. Finally, we demonstrate that CD22(-/-) splenic B cells proliferate independently of BOB.1/OBF1 upon stimulation with LPS. These studies suggest that the B cell differentiation defect observed in BOB.1/OBF.1(-/-) mice is BCR-signal dependent. However, the impairment in germinal center formation is caused by a different mechanism. PB - Wiley-V C H Verlag Gmbh, Weinheim T2 - European Journal of Immunology T1 - CD22 regulates early B cell development in BOB.1/OBF.1-deficient mice EP - 2489 IS - 9 SP - 2481 VL - 32 DO - 10.1002/1521-4141(200209)32:9_2481::AID-IMMU2481>3.0.CO;2-C ER -
@article{ author = "Samardžić, T. and Gerlach, J and Muller, K and Marinković, Dragan and Hess, J and Nitschke, L. and Wirth, Thomas", year = "2002", abstract = "BOB.1/OBF1 (also called OCA-B), a B lymphocyte-specific transcriptional coactivator, is recruited to octamer-containing promoters by interacting with the Oct-1 or Oct-2 proteins. BOB.1/OBF.1-deficient mice show impaired secondary immunoglobulin isotype secretion and complete absence of germinal centers. Furthermore, numbers of splenic B cells are reduced due to a developmental block at the transitional B cell stage in the bone marrow. We found that surface expression of CD22 is selectively increased on B lineage cells in the bone marrow of BOB.1/OBF.1-deficient mice. CD22 is known as a negative regulator of B cell receptor signaling. We therefore investigated whether defects in B cell development in the BOB.1/OBF1-deficient mice might be due to CD22 up-regulation. Mice were generated lacking both genes. In BOB.1/OBF.1 xCD22 double-deficient mice, numbers of transitional B cells in the bone marrow were normal. Consequently, double-deficient mice also had normal B to T cell ratios in the spleen. We show that BOB.1/OBF.1(-/-) B cells were incapable to induce BCR-triggered Ca2+ mobilization. This Ca2+-signalling defect was restored in BOBA/ OBF1 xCD22 double-deficient B cells. Nevertheless, double-deficient animals were unable to mount humoral immune responses and to form germinal centers. Finally, we demonstrate that CD22(-/-) splenic B cells proliferate independently of BOB.1/OBF1 upon stimulation with LPS. These studies suggest that the B cell differentiation defect observed in BOB.1/OBF.1(-/-) mice is BCR-signal dependent. However, the impairment in germinal center formation is caused by a different mechanism.", publisher = "Wiley-V C H Verlag Gmbh, Weinheim", journal = "European Journal of Immunology", title = "CD22 regulates early B cell development in BOB.1/OBF.1-deficient mice", pages = "2489-2481", number = "9", volume = "32", doi = "10.1002/1521-4141(200209)32:9_2481::AID-IMMU2481>3.0.CO;2-C" }
Samardžić, T., Gerlach, J., Muller, K., Marinković, D., Hess, J., Nitschke, L.,& Wirth, T.. (2002). CD22 regulates early B cell development in BOB.1/OBF.1-deficient mice. in European Journal of Immunology Wiley-V C H Verlag Gmbh, Weinheim., 32(9), 2481-2489. https://doi.org/10.1002/1521-4141(200209)32:9_2481::AID-IMMU2481>3.0.CO;2-C
Samardžić T, Gerlach J, Muller K, Marinković D, Hess J, Nitschke L, Wirth T. CD22 regulates early B cell development in BOB.1/OBF.1-deficient mice. in European Journal of Immunology. 2002;32(9):2481-2489. doi:10.1002/1521-4141(200209)32:9_2481::AID-IMMU2481>3.0.CO;2-C .
Samardžić, T., Gerlach, J, Muller, K, Marinković, Dragan, Hess, J, Nitschke, L., Wirth, Thomas, "CD22 regulates early B cell development in BOB.1/OBF.1-deficient mice" in European Journal of Immunology, 32, no. 9 (2002):2481-2489, https://doi.org/10.1002/1521-4141(200209)32:9_2481::AID-IMMU2481>3.0.CO;2-C . .