Biology subjects

Bottermann, M.

Publications and source records attributed to Bottermann, M..

3 recordsLinked to original sources

bioRxiv2026

A Germinal Center-Independent Innate-Like Memory B Cell Compartment of B1 Origin

Memory B cells (MBCs) are a critical cellular reservoir for long-term humoral immunity. MBCs display heterogeneous isotypes and surface markers and can arise through both germinal center (GC)-dependent and GC-independent extrafollicular (EF) pathways. Both the mechanisms controlling EF MBC differentiation and the identities of the B cell populations from which EF MBCs derive remain poorly understood. To capture MBC diversity, we applied a broad selection strategy followed by transcriptional profiling, identifying a subset of MBCs characterized by minimal class switching, limited somatic hypermutation, and an innate-like gene signature. Using genetic models, we demonstrated that this subset arises independently of GC responses and derives from innate B1 cells. These innate-like MBCs differentiate into antigen-specific antibody-secreting cells and confer protection against lethal viral infection. Together, our findings define a previously unrecognized arm of MBC responses, demonstrating that innate B1 cells contribute a non-redundant antibody repertoire to protective immunological memory.

immunology↗

bioRxiv2025

Rapid acquisition of HIV-1 neutralization breadth in a rhesus V2 apex germline antibody mouse model after a single bolus immunization

Current vaccine strategies to elicit broadly neutralizing antibodies (bnAbs) against HIV-1 generally propose complex, multi-boost immunization regimens. In rhesus macaques, SHIV infection has been observed to rapidly drive the development of some classes of bnAbs that share structural similarities with those in humans. Here, we generated a knockin mouse model with B cells bearing the unmutated common ancestor (UCA) of the V2 apex-targeted bnAb lineage, V033-a. A single immunization of mice with a germline-targeting native-like trimer was sufficient to recapitulate the ontogeny of the mature rhesus bnAb in knockin mice--including rare, disfavored somatic mutations--leading to the induction of antibodies that exhibited potent neutralization against both autologous and heterologous tier 2 viruses. A boost with Env escape mutant trimers further improved breadth and potency, and cryo-EM structure revealed the structural basis for heterologous neutralization breadth. Non-human primate and mouse models can thus combine with structure to serve as a platform for identifying and confirming immunogens that streamline HIV-vaccination regimens.

immunology↗

bioRxiv2024

Functional and epitope specific monoclonal antibody discovery directly from immune sera using cryoEM

Antibodies are crucial therapeutics, comprising a significant portion of approved drugs due to their safety and clinical efficacy. Traditional antibody discovery methods are labor-intensive, limiting scalability and high-throughput analysis. Here, we improved upon our streamlined approach combining structural analysis and bioinformatics to infer heavy and light chain sequences from electron potential maps of serum-derived polyclonal antibodies (pAbs) bound to antigens. Using ModelAngelo, an automated structure-building tool, we accelerated pAb sequence determination and identified sequence matches in B cell repertoires via ModelAngelo derived Hidden Markov Models (HMMs) associated with pAb structures. Benchmarking against results from a non-human primate HIV vaccine trial, our pipeline reduced analysis time from weeks to under a day with higher precision. Validation with murine immune sera from influenza vaccination revealed multiple protective antibodies. This workflow enhances antibody discovery, enabling faster, more accurate mapping of polyclonal responses with broad applications in vaccine development and therapeutic antibody discovery.

immunology↗