CD11c+ T-bet+ B Cells Require IL-21 and IFN-γ from Type 1 T Follicular Helper Cells and Intrinsic Bcl-6 Expression but Develop Normally in the Absence of T-bet

Levack, Russell C.; Newell, Krista L; Popescu, Maria; Cabrera-Martinez, Berenice; Winslow, Gary M.

doi:10.4049/jimmunol.2000206

Cited by 35 publications

(62 citation statements)

References 59 publications

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“…Indeed, severe disruption of lymphatic tissue organization and germinal center formation have been observed in severe COVID-19 cases [ 19 ]. Moreover, studies from our laboratory have shown that follicle architecture disruption, acute plasmablast expansion, and type-1 cytokine skewing occurs during murine intracellular bacterial infection [ 20 – 22 ]. We observed IgM + memory to be protective during E .…”

Section: Discussionmentioning

confidence: 99%

Switched and unswitched memory B cells detected during SARS-CoV-2 convalescence correlate with limited symptom duration

et al. 2021

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Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of the pandemic human respiratory illness COVID-19, is a global health emergency. While severe acute disease has been linked to an expansion of antibody-secreting plasmablasts, we sought to identify B cell responses that correlated with positive clinical outcomes in convalescent patients. We characterized the peripheral blood B cell immunophenotype and plasma antibody responses in 40 recovered non-hospitalized COVID-19 subjects that were enrolled as donors in a convalescent plasma treatment study. We observed a significant negative correlation between the frequency of peripheral blood memory B cells and the duration of symptoms for convalescent subjects. Memory B cell subsets in convalescent subjects were composed of classical CD24+ class-switched memory B cells, but also activated CD24-negative and natural unswitched CD27+ IgD+ IgM+ subsets. Memory B cell frequency was significantly correlated with both IgG1 and IgM responses to the SARS-CoV-2 spike protein receptor binding domain (RBD) in most seropositive subjects. IgM+ memory, but not switched memory, directly correlated with virus-specific antibody responses, and remained stable over 3 months. Our findings suggest that the frequency of memory B cells is a critical indicator of disease resolution, and that IgM+ memory B cells may play an important role in SARS-CoV-2 immunity.

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Section: Discussionmentioning

confidence: 99%

Switched and unswitched memory B cells detected during SARS-CoV-2 convalescence correlate with limited symptom duration

et al. 2021

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“…T FH 2 cells, but not T FH 1 and T FH 17 cells, have been identified to promote IgE secretion from B cells 21 . It is now coming to the surface that the antigen type impacts the differentiation of T FH cells 22,53,63,64 . For example, T FH 1 cells are generated during human immunodeficiency virus and Ehrlichia muris infection, 63 whereas T FH 2 and T FH 13 cells are induced during allergen sensitization 22 .…”

Section: Development Phenotype and Role Of Tfh Cellsmentioning

confidence: 99%

“…It is now coming to the surface that the antigen type impacts the differentiation of T FH cells 22,53,63,64 . For example, T FH 1 cells are generated during human immunodeficiency virus and Ehrlichia muris infection, 63 whereas T FH 2 and T FH 13 cells are induced during allergen sensitization 22 . The discovery of dual transcription factor‐expressing or cytokine‐producing T FH cells indicates the plasticity and functional complexity of T FH cells 22,53,63,64 .…”

Section: Development Phenotype and Role Of Tfh Cellsmentioning

confidence: 99%

“…For example, T FH 1 cells are generated during human immunodeficiency virus and Ehrlichia muris infection, 63 whereas T FH 2 and T FH 13 cells are induced during allergen sensitization 22 . The discovery of dual transcription factor‐expressing or cytokine‐producing T FH cells indicates the plasticity and functional complexity of T FH cells 22,53,63,64 . These dual transcription factor‐expressing or cytokine‐producing T FH cells play a specific role in dictating selective features of GC reaction.…”

Section: Development Phenotype and Role Of Tfh Cellsmentioning

confidence: 99%

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Roles of follicular helper and regulatory T cells in allergic diseases and allergen immunotherapy

Yao

Chen

et al. 2020

Allergy

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Allergic diseases are characterized by overactive type 2 immune responses to allergens and immunoglobulin E (IgE)‐mediated hypersensitivity. Emerging evidence suggests that follicular helper T (TFH) cells, rather than type 2 T‐helper (TH2) cells, play a crucial role in controlling IgE production. However, follicular regulatory T (TFR) cells, a specialized subset of regulatory T (TREG) cells resident in B‐cell follicles, restricts TFH cell‐mediated help in extrafollicular antibody production, germinal center (GC) formation, immunoglobulin affinity maturation, and long‐lived, high‐affinity plasma and memory B‐cell differentiation. In mouse models of allergic asthma and food allergy, CXCR5+ TFH cells, not CXCR5− conventional TH2 cells, are needed to support IgE production, otherwise exacerbated by CXCR5+ TFR cell deletion. Upregulation of TFH cell activities, including a skewing toward type 2 TFH (TFH2) and IL‐13 producing TFH (TFH13) phenotypes, and defects in TFR cells have been identified in patients with allergic diseases. Allergen immunotherapy (AIT) reinstates the balance between TFH and TFR cells in patients with allergic diseases, resulting in clinical benefits. Collectively, further understanding of TFH and TFR cells and their role in the immunopathogenesis of allergic diseases creates opportunities to develop novel therapeutic approaches.

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“…Differences in chemokine receptor expression by memory B cell subsets may facilitate their differential trafficking ability and accumulation outside of the lymph node and in non‐lymphoid tissues. T‐bet + atMBCs and DN2 B cells have low surface expression of CXCR5 critical to lymph node homing and entry to the B cell follicle, instead expressing high levels of the inflammatory tissue‐homing marker CXCR3 and the integrin CD11c 22,54,96,97 . As a result, T‐bet + B cells are largely absent from lymph nodes but identifiable in the blood, bone marrow, and spleen 34 where they localize at the T:B cell border 97 and can become resident, losing the ability to recirculate 48 .…”

Section: Memory In Peripheral Tissuesmentioning

confidence: 99%

Human antiviral B cell responses: Emerging lessons from hepatitis B and COVID‐19

Burton¹,

Maini²

2021

Immunological Reviews

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Humoral immunity is a critical component of the coordinated response required to resolve viral infections and mediate protection following pathogen clearance or vaccination. A better understanding of factors shaping the memory B cell response will allow tailored development of efficient preventative vaccines against emerging acute viral infections, therapeutic vaccines, and immunotherapies for chronic viral infections. Here, we use recent data obtained by profiling antigen‐specific B cell responses in hepatitis B as a framework to explore lessons that can be learnt from different viral infections about the diverse influences on humoral immunity. Hepatitis B provides a paradigm where successful B cell responses in resolved or vaccinated individuals can be contrasted to the failed response in chronic infection, while also exemplifying the degree to which B cell responses within infected individuals can differ to two antigens from the same virus. Drawing on studies in other human and murine infections, including emerging data from COVID‐19, we consider the influence of antigen quantity and structure on the quality of the B cell response, the role of differential CD4 help, the importance of germinal center vs extrafollicular responses and the emerging concept that responses residing in non‐lymphoid organs can participate in B cell memory.

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CD11c+ T-bet+ B Cells Require IL-21 and IFN-γ from Type 1 T Follicular Helper Cells and Intrinsic Bcl-6 Expression but Develop Normally in the Absence of T-bet

Cited by 35 publications

References 59 publications

Switched and unswitched memory B cells detected during SARS-CoV-2 convalescence correlate with limited symptom duration

Switched and unswitched memory B cells detected during SARS-CoV-2 convalescence correlate with limited symptom duration

Roles of follicular helper and regulatory T cells in allergic diseases and allergen immunotherapy

Human antiviral B cell responses: Emerging lessons from hepatitis B and COVID‐19

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