Details

Autor(en) / Beteiligte

• Peterson, Jacob N
• Boackle, Susan A
• Taitano, Sophina H
• Sang, Allison
• Lang, Julie
• Kelly, Margot
• Rahkola, Jeremy T
• Miranda, Anjelica M
• Sheridan, Ryan M
• Thurman, Joshua M
• Rao, V Koneti
• Torres, Raul M
• Pelanda, Roberta

Titel

Elevated Detection of Dual Antibody B Cells Identifies Lupus Patients With B Cell-Reactive VH4-34 Autoantibodies

Ist Teil von

• Frontiers in immunology, 2022-02, Vol.13, p.795209-795209

Ort / Verlag

Switzerland: Frontiers Media S.A

Erscheinungsjahr

2022

Quelle

MEDLINE

Beschreibungen/Notizen

• About 5% of B cells in healthy mice and humans are allelically or isotypically included and hence co-express two different antibodies. In mice, dual antibody B cells (B ) expand with systemic autoimmunity, co-express autoreactive and non-autoreactive antibodies, and participate in immune responses, but this phenomenon is strain dependent. This study was developed with two goals: 1) to establish the contribution of TLR and IFN receptor signaling to the development of germinal center B cells that express two antibodies in MRL/ mice; and 2) to determine whether B B cells are increased and particularly activated in a subset of adult patients diagnosed with systemic lupus erythematosus (SLE). Results from the MRL/ studies indicate that the enhanced differentiation of dual-κ B cells into germinal center B cells is due to a heightened response to TLR7 and TLR9 signaling, further fueled by an increased response to type II IFN. To understand the clinical and translational implications of our observations in mouse B B cells, cohorts of SLE patients and healthy controls were recruited and evaluated for expression of dual BCRs. Results from flow cytometry and microscopy revealed supraphysiological frequencies of κ λ B cells in one fourth of the SLE patients. Abnormal numbers of κ λ B cells correlated with higher frequencies of activated naïve B cells and age-associated B cells, and a lower proportion of "B cells that are naïve IgD " (BND). However, results from single cell V(D)J sequencing demonstrated that these high κ λ SLE patients harbored normal frequencies of κ λ and other B B cells. and we further show that their B cells were instead decorated by κ and λ VH4-34 autoantibodies. Thus, our findings indicate that elevated flow cytometric detection of isotypically-included B cells can identify patients with high titers of B cell-reactive VH4-34 autoantibodies and abnormal distribution of B cell subsets relevant to autoimmunity.