Tailoring Immune Responses toward Autoimmunity: Transcriptional Regulators That Drive the Creation and Collusion of Autoreactive Lymphocytes
T-dependent humoral immune responses to infection involve a collaboration between B and CD4 T cell activation, migration, and co-stimulation, thereby culminating in the formation of germinal centers (GCs) and eventual differentiation into memory cells and long-lived plasma cells (PCs). CD4 T cell-de...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2018-03-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00482/full |
| _version_ | 1818109886383259648 |
|---|---|
| author | Kim L. Good-Jacobson Kim L. Good-Jacobson Joanna R. Groom Joanna R. Groom |
| author_facet | Kim L. Good-Jacobson Kim L. Good-Jacobson Joanna R. Groom Joanna R. Groom |
| author_sort | Kim L. Good-Jacobson |
| collection | DOAJ |
| description | T-dependent humoral immune responses to infection involve a collaboration between B and CD4 T cell activation, migration, and co-stimulation, thereby culminating in the formation of germinal centers (GCs) and eventual differentiation into memory cells and long-lived plasma cells (PCs). CD4 T cell-derived signals drive the formation of a tailored B cell response. Downstream of these signals are transcriptional regulators that are the critical enactors of immune cell programs. In particular, a core group of transcription factors regulate both B and T cell differentiation, identity, and function. The timing and expression levels of these transcription factors are tightly controlled, with dysregulated expression correlated to immune cell dysfunction in autoimmunity and lymphomagenesis. Recent studies have significantly advanced our understanding of both extrinsic and intrinsic regulators of autoreactive B cells and antibody-secreting PCs in systemic lupus erythematosus, rheumatoid arthritis, and other autoimmune conditions. Yet, there are still gaps in our understanding of the causative role these regulators play, as well as the link between lymphoid responses and peripheral damage. This review will focus on the genesis of immunopathogenic CD4 helper and GC B cells. In particular, we will detail the transcriptional regulation of cytokine and chemokine receptor signaling during the pathogenesis of GC-derived autoimmune conditions in both murine models and human patients. |
| first_indexed | 2024-12-11T02:38:23Z |
| format | Article |
| id | doaj.art-c5c8fe4d628f4f40920f7e74224fc292 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T02:38:23Z |
| publishDate | 2018-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-c5c8fe4d628f4f40920f7e74224fc2922022-12-22T01:23:39ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-03-01910.3389/fimmu.2018.00482338976Tailoring Immune Responses toward Autoimmunity: Transcriptional Regulators That Drive the Creation and Collusion of Autoreactive LymphocytesKim L. Good-Jacobson0Kim L. Good-Jacobson1Joanna R. Groom2Joanna R. Groom3Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, AustraliaInfection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, VIC, AustraliaWalter and Eliza Hall Institute of Medical Research, Parkville, VIC, AustraliaDepartment of Medical Biology, University of Melbourne, Parkville, VIC, AustraliaT-dependent humoral immune responses to infection involve a collaboration between B and CD4 T cell activation, migration, and co-stimulation, thereby culminating in the formation of germinal centers (GCs) and eventual differentiation into memory cells and long-lived plasma cells (PCs). CD4 T cell-derived signals drive the formation of a tailored B cell response. Downstream of these signals are transcriptional regulators that are the critical enactors of immune cell programs. In particular, a core group of transcription factors regulate both B and T cell differentiation, identity, and function. The timing and expression levels of these transcription factors are tightly controlled, with dysregulated expression correlated to immune cell dysfunction in autoimmunity and lymphomagenesis. Recent studies have significantly advanced our understanding of both extrinsic and intrinsic regulators of autoreactive B cells and antibody-secreting PCs in systemic lupus erythematosus, rheumatoid arthritis, and other autoimmune conditions. Yet, there are still gaps in our understanding of the causative role these regulators play, as well as the link between lymphoid responses and peripheral damage. This review will focus on the genesis of immunopathogenic CD4 helper and GC B cells. In particular, we will detail the transcriptional regulation of cytokine and chemokine receptor signaling during the pathogenesis of GC-derived autoimmune conditions in both murine models and human patients.http://journal.frontiersin.org/article/10.3389/fimmu.2018.00482/fullautoreactive B cellsgerminal centerstranscription factorsBcl-6T-betinterferon-gamma |
| spellingShingle | Kim L. Good-Jacobson Kim L. Good-Jacobson Joanna R. Groom Joanna R. Groom Tailoring Immune Responses toward Autoimmunity: Transcriptional Regulators That Drive the Creation and Collusion of Autoreactive Lymphocytes Frontiers in Immunology autoreactive B cells germinal centers transcription factors Bcl-6 T-bet interferon-gamma |
| title | Tailoring Immune Responses toward Autoimmunity: Transcriptional Regulators That Drive the Creation and Collusion of Autoreactive Lymphocytes |
| title_full | Tailoring Immune Responses toward Autoimmunity: Transcriptional Regulators That Drive the Creation and Collusion of Autoreactive Lymphocytes |
| title_fullStr | Tailoring Immune Responses toward Autoimmunity: Transcriptional Regulators That Drive the Creation and Collusion of Autoreactive Lymphocytes |
| title_full_unstemmed | Tailoring Immune Responses toward Autoimmunity: Transcriptional Regulators That Drive the Creation and Collusion of Autoreactive Lymphocytes |
| title_short | Tailoring Immune Responses toward Autoimmunity: Transcriptional Regulators That Drive the Creation and Collusion of Autoreactive Lymphocytes |
| title_sort | tailoring immune responses toward autoimmunity transcriptional regulators that drive the creation and collusion of autoreactive lymphocytes |
| topic | autoreactive B cells germinal centers transcription factors Bcl-6 T-bet interferon-gamma |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00482/full |
| work_keys_str_mv | AT kimlgoodjacobson tailoringimmuneresponsestowardautoimmunitytranscriptionalregulatorsthatdrivethecreationandcollusionofautoreactivelymphocytes AT kimlgoodjacobson tailoringimmuneresponsestowardautoimmunitytranscriptionalregulatorsthatdrivethecreationandcollusionofautoreactivelymphocytes AT joannargroom tailoringimmuneresponsestowardautoimmunitytranscriptionalregulatorsthatdrivethecreationandcollusionofautoreactivelymphocytes AT joannargroom tailoringimmuneresponsestowardautoimmunitytranscriptionalregulatorsthatdrivethecreationandcollusionofautoreactivelymphocytes |