OCA-B (Oct coactivator from B cells) is a B-cell specific coactivator of transcription that acts in conjunction with the ubiquitously expressed activator, OCT-1 or the B cell-restricted OCT-2. OCT-1 or OCT-2 can bind an upstream octamer element with the consensus sequence 5'-ATGCAAAT-3' in target gene promoters and enhancers. At the octamer element, the OCT-1/2-OCA-B complex is able to regulate gene expression via interaction with the basal transcription machinery. OCA-B was originally identified as a nuclear transcriptional coactivator and then shown to be essential for antigen-driven immune responses, including secondary isotype expression, germinal center formation and BCR dependent proliferation. These defects contribute to the severely impaired antigen-dependent immune responses of Oca-b-/- mice. The later identification of a membrane-bound, myristoylated form of OCA-B suggested additional, potentially unique functions in B cell signaling pathways and that OCA-B might function through both transcriptional and non-transcriptional mechanisms within the cell. Therefore, a strong focus was placed on identifying additional OCA-B target genes that could explain its role in the antigen-dependent immune response. Importantly, this study has identified, by cDNA microarray, several genes that fail to be up regulated in the Oca-b-/- activated B cells. OCA-B deficient cells have a compromised response to BCR signaling and many of the identified OCA-B target genes (e.g. Kcnn4, Lck, CyclinD3, and Cdc37) play important roles in cell signaling; however, their specific functions in B cell development and activation are largely unknown. From multiple primary B cell stages, we have found that key OCA-B target genes are expressed and regulated throughout B cell development. This study has identified a novel developmental block in Oca-b-/- mice, which indicates that OCA-B also functions in the pre-B1 to pre-B2 cell transition by mediating pre-BCR signaling. Most surprisingly, OCA-B directly interacts with SYK, a tyrosine kinase critical for pre-BCR and BCR signaling. This unprecedented type of interaction — of a transcriptional coactivator with a signaling kinase — takes place in the cytoplasm and directly regulates SYK stability. Combined with the deregulation of OCA-B target genes, this may help explain both previously observed defects in the antigen-dependent immune response of Oca-b-/- mice and newly identified defects in early B cell development. This study indicates that OCA-B is required for a complete response to pre-BCR and BCR signaling at multiple stages of B cell development, through its non-transcriptional regulation of SYK.
","abstract_html":"<p>OCA-B (Oct coactivator from B cells) is a B-cell specific coactivator of transcription that acts in conjunction with the ubiquitously expressed activator, OCT-1 or the B cell-restricted OCT-2. OCT-1 or OCT-2 can bind an upstream octamer element with the consensus sequence 5'-ATGCAAAT-3' in target gene promoters and enhancers. At the octamer element, the OCT-1/2-OCA-B complex is able to regulate gene expression via interaction with the basal transcription machinery. OCA-B was originally identified as a nuclear transcriptional coactivator and then shown to be essential for antigen-driven immune responses, including secondary isotype expression, germinal center formation and BCR dependent proliferation. These defects contribute to the severely impaired antigen-dependent immune responses of Oca-b-/- mice. The later identification of a membrane-bound, myristoylated form of OCA-B suggested additional, potentially unique functions in B cell signaling pathways and that OCA-B might function through both transcriptional and non-transcriptional mechanisms within the cell. Therefore, a strong focus was placed on identifying additional OCA-B target genes that could explain its role in the antigen-dependent immune response. Importantly, this study has identified, by cDNA microarray, several genes that fail to be up regulated in the Oca-b-/- activated B cells. OCA-B deficient cells have a compromised response to BCR signaling and many of the identified OCA-B target genes (e.g. Kcnn4, Lck, CyclinD3, and Cdc37) play important roles in cell signaling; however, their specific functions in B cell development and activation are largely unknown. From multiple primary B cell stages, we have found that key OCA-B target genes are expressed and regulated throughout B cell development. This study has identified a novel developmental block in Oca-b-/- mice, which indicates that OCA-B also functions in the pre-B1 to pre-B2 cell transition by mediating pre-BCR signaling. Most surprisingly, OCA-B directly interacts with SYK, a tyrosine kinase critical for pre-BCR and BCR signaling. This unprecedented type of interaction — of a transcriptional coactivator with a signaling kinase — takes place in the cytoplasm and directly regulates SYK stability. Combined with the deregulation of OCA-B target genes, this may help explain both previously observed defects in the antigen-dependent immune response of Oca-b-/- mice and newly identified defects in early B cell development. This study indicates that OCA-B is required for a complete response to pre-BCR and BCR signaling at multiple stages of B cell development, through its non-transcriptional regulation of SYK.</p>","abstract_has_math":false,"creators":["Siegel, Rachael"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Thesis","degree_discipline":null,"degree_department":null,"school":null,"contributors":["Robert G. Roeder"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2006,"date_issued":"2006-01-01T08:00:00Z","date_published":"2006-01-01T08:00:00Z","updated_at":"2026-07-24T04:10:53Z","subjects":["B cell development","OCA-B","B cell receptor signaling","Life Sciences"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/62","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Robert G. Roeder"]},{"key":"dc:creator","label":"Author","values":["Siegel, Rachael"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"thesis:degree_level","label":"Degree Level","values":["Thesis"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["B cell development","OCA-B","B cell receptor signaling","Life Sciences"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/62"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["OCA-B (Oct coactivator from B cells) is a B-cell specific coactivator of transcription that acts in conjunction with the ubiquitously expressed activator, OCT-1 or the B cell-restricted OCT-2. OCT-1 or OCT-2 can bind an upstream octamer element with the consensus sequence 5'-ATGCAAAT-3' in target gene promoters and enhancers. At the octamer element, the OCT-1/2-OCA-B complex is able to regulate gene expression via interaction with the basal transcription machinery. OCA-B was originally identified as a nuclear transcriptional coactivator and then shown to be essential for antigen-driven immune responses, including secondary isotype expression, germinal center formation and BCR dependent proliferation. These defects contribute to the severely impaired antigen-dependent immune responses of Oca-b-/- mice. The later identification of a membrane-bound, myristoylated form of OCA-B suggested additional, potentially unique functions in B cell signaling pathways and that OCA-B might function through both transcriptional and non-transcriptional mechanisms within the cell. Therefore, a strong focus was placed on identifying additional OCA-B target genes that could explain its role in the antigen-dependent immune response. Importantly, this study has identified, by cDNA microarray, several genes that fail to be up regulated in the Oca-b-/- activated B cells. OCA-B deficient cells have a compromised response to BCR signaling and many of the identified OCA-B target genes (e.g. Kcnn4, Lck, CyclinD3, and Cdc37) play important roles in cell signaling; however, their specific functions in B cell development and activation are largely unknown. From multiple primary B cell stages, we have found that key OCA-B target genes are expressed and regulated throughout B cell development. This study has identified a novel developmental block in Oca-b-/- mice, which indicates that OCA-B also functions in the pre-B1 to pre-B2 cell transition by mediating pre-BCR signaling. Most surprisingly, OCA-B directly interacts with SYK, a tyrosine kinase critical for pre-BCR and BCR signaling. This unprecedented type of interaction — of a transcriptional coactivator with a signaling kinase — takes place in the cytoplasm and directly regulates SYK stability. Combined with the deregulation of OCA-B target genes, this may help explain both previously observed defects in the antigen-dependent immune response of Oca-b-/- mice and newly identified defects in early B cell development. This study indicates that OCA-B is required for a complete response to pre-BCR and BCR signaling at multiple stages of B cell development, through its non-transcriptional regulation of SYK.
"]},{"key":"dc:title","label":"Title","values":["The Dual Role of OCA-B in B Cell Development and Signaling"]}]}],"canonical_facts":{"dc:contributor":["Robert G. Roeder"],"dc:creator":["Siegel, Rachael"],"dc:description.abstract":["OCA-B (Oct coactivator from B cells) is a B-cell specific coactivator of transcription that acts in conjunction with the ubiquitously expressed activator, OCT-1 or the B cell-restricted OCT-2. OCT-1 or OCT-2 can bind an upstream octamer element with the consensus sequence 5'-ATGCAAAT-3' in target gene promoters and enhancers. At the octamer element, the OCT-1/2-OCA-B complex is able to regulate gene expression via interaction with the basal transcription machinery. OCA-B was originally identified as a nuclear transcriptional coactivator and then shown to be essential for antigen-driven immune responses, including secondary isotype expression, germinal center formation and BCR dependent proliferation. These defects contribute to the severely impaired antigen-dependent immune responses of Oca-b-/- mice. The later identification of a membrane-bound, myristoylated form of OCA-B suggested additional, potentially unique functions in B cell signaling pathways and that OCA-B might function through both transcriptional and non-transcriptional mechanisms within the cell. Therefore, a strong focus was placed on identifying additional OCA-B target genes that could explain its role in the antigen-dependent immune response. Importantly, this study has identified, by cDNA microarray, several genes that fail to be up regulated in the Oca-b-/- activated B cells. OCA-B deficient cells have a compromised response to BCR signaling and many of the identified OCA-B target genes (e.g. Kcnn4, Lck, CyclinD3, and Cdc37) play important roles in cell signaling; however, their specific functions in B cell development and activation are largely unknown. From multiple primary B cell stages, we have found that key OCA-B target genes are expressed and regulated throughout B cell development. This study has identified a novel developmental block in Oca-b-/- mice, which indicates that OCA-B also functions in the pre-B1 to pre-B2 cell transition by mediating pre-BCR signaling. Most surprisingly, OCA-B directly interacts with SYK, a tyrosine kinase critical for pre-BCR and BCR signaling. This unprecedented type of interaction — of a transcriptional coactivator with a signaling kinase — takes place in the cytoplasm and directly regulates SYK stability. Combined with the deregulation of OCA-B target genes, this may help explain both previously observed defects in the antigen-dependent immune response of Oca-b-/- mice and newly identified defects in early B cell development. This study indicates that OCA-B is required for a complete response to pre-BCR and BCR signaling at multiple stages of B cell development, through its non-transcriptional regulation of SYK.
"],"dc:identifier":["https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/62"],"dc:subject":["B cell development","OCA-B","B cell receptor signaling","Life Sciences"],"dc:title":["The Dual Role of OCA-B in B Cell Development and Signaling"],"thesis:degree_level":["Thesis"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T04:10:53Z"}