Biology subjects

Grigorova, I. L.

Publications and source records attributed to Grigorova, I. L..

5 recordsLinked to original sources

bioRxiv2025

BCR repertoire analysis and cloning of antibody candidates targeting native and Asp7-isomerized beta-amyloid

Computational approaches are increasingly used to predict monoclonal antibody (mAb) candidates from BCR-seq datasets. However, the reliable identification of B cells encoding antibodies against rare antigenic epitopes remains challenging. We employed a repertoire-guided workflow combining antigen-tetramer sorting of B cells from immunized mice, followed by low-input bulk BCR-seq yielding informative clonal repertoires. Clustering and supporting somatic hypermutation (SHM) lineage analysis allowed us to identify IGH and IGK clonotypes potentially targeting {beta}-amyloid and its isoAsp7 variant (isoD7-A{beta}1-16), implicated in Alzheimers disease. We observed recurrent IGHV8-12 and IGKV1-117 usage, consistent with canonical mouse anti-A{beta} responses. Focusing on isoD7-A{beta} binders, we selected ten candidate IGH-IGK pairs for recombinant expression. One recombinant mAb demonstrated preferential binding to isoD7-A{beta} by microscale thermophoresis, supporting the feasibility of the approach but underscoring the challenge of accurate chain pairing. This highlights the potential of bioinformatic workflows to identify mAbs even under low-input conditions.

immunology↗

bioRxiv2022

Nuclear proteins acquiring Germinal Center B cells are specifically suppressed by follicular regulatory T cells.

Follicular regulatory T cells (Tfrs) restrict development of autoantibodies and autoimmunity while supporting high-affinity foreign antigen-specific humoral response. However, whether Tfrs can directly repress germinal center (GC) B cells that acquire auto-antigens is unclear. Moreover, TCR specificity of Tfrs to self-antigens is not known. Our study suggests that nuclear proteins contain antigens specific to Tfrs. Targeting of these proteins to antigen-specific B cells triggers rapid accumulation of Tfrs with immunosuppressive characteristics. Tfrs then exert negative regulation of GC B cells with predominant inhibition of the nuclear protein-acquiring GC B cells, suggesting an important role of direct cognate Tfr-GC B cells interactions for the control of effector B cell response.

immunology↗

bioRxiv2018

B cells transiently exposed to antigen that return to quiescence respond to protein immunization similarly to naive B cells

Transient exposure of B cells to moderately multivalent antigens has been shown to lead to their activation and recruitment into T-dependent B cell response in the presence of T cell help. However, when T cell help is delayed, transiently activated B cells return to a naive-like state. While B cells that briefly encountered cognate antigen and then underwent inactivation are not tolerant, whether they may be hypo-or hyper-responsive to cognate antigen is not known. In this study we show that naive B cells and those previously exposed to antigen and then inactivated generate comparable germinal center and plasma cell responses after immunization with a wide range of antigen concentrations.

immunology↗

bioRxiv2018

B cell receptor crosslinking can augment T cell help-mediated germinal center B cell selection.

Selection of germinal center (GC) B cells with B cell receptors (BCR) possessing high affinity to foreign antigen (Ag) and their differentiation into antibody-secreting long-lived plasma cells is critical for potent long-term humoral immunity. Ag-dependent engagement of GC B cell BCR triggers Ag internalization and loading of antigenic peptides on MHCII molecules for presentation to follicular helper T cells (Tfh) and acquisition of T cell help. However, whether it also provides signals that are critical or synergistic with T cell help for GC B cell selection and differentiation in vivo is not known. Here we show that T cell help is sufficient to induce GC B cell expansion and plasmablast (PB) formation in the absence of recurrent BCR engagement with Ag. Ag-mediated BCR crosslinking on the other hand is not sufficient to promote GC B cell selection, but can synergize with T cell help to enhance the GC B cell and PB responses when T cell help is limiting.

immunology↗

bioRxiv2018

CCL3 promotes germinal center B cells sampling by follicular regulatory T cells and ensures optimal humoral response

Previous studies and our findings suggest upregulated expression of proinflammatory chemokines CCL3/4 in germinal center (GC) centrocytes. However, the role of CCL3/4 for centrocyte interactions with follicular T cells and regulation of humoral immunity is poorly understood. We found that CCL3 promotes chemotaxis of Tfr cells ex vivo. In vivo CCL3 is not required for Tfr cells recruitment of into the GC light zone. However, B cells-intrinsic production of CCL3 promotes their direct interactions and negative regulation by follicular regulatory T cells (Tfr) within GCs.

immunology↗