An Engineered Mouse Model That Generates a Diverse Repertoire of Endogenous, High-Affinity Common Light Chain Antibodies.

Antibodies (Basel)

23andMe, Inc. Therapeutics, 349 Oyster Point Boulevard, South San Francisco, CA 94080, USA.

Published: February 2024

Bispecific antibodies have gained increasing popularity as therapeutics as they enable novel activities that cannot be achieved with monospecific antibodies. Some of the most popular bispecific formats are molecules in which two Fab arms with different antigen specificities are combined into one IgG-like molecule. One way to produce these bispecific molecules requires the discovery of antibodies against the two antigens of interest that share a common light chain. Here, we present the generation and characterization of a common light chain mouse model, in which the endogenous IGKJ cluster is replaced with a prearranged, modified murine IGKV10-96/IGKJ1 segment. We demonstrate that genetic modification does not impact B-cell development. Upon immunization with ovalbumin, the animals generate an antibody repertoire with VH gene segment usage of a similar diversity to wildtype mice, while the light chain diversity is restricted to antibodies derived from the prearranged IGKV10-96/IGKJ1 germline. We further show that the clonotype diversity of the common light chain immune repertoire matches the diversity of immune repertoire isolated from wildtype mice. Finally, the common light chain anti-ovalbumin antibodies have only slightly lower affinities than antibodies isolated from wildtype mice, demonstrating the suitability of these animals for antibody discovery for bispecific antibody generation.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10885109PMC
http://dx.doi.org/10.3390/antib13010014DOI Listing

Publication Analysis

Top Keywords

light chain
24
common light
20
wildtype mice
12
mouse model
8
immune repertoire
8
isolated wildtype
8
antibodies
7
light
6
chain
6
common
5

Similar Publications

Background & Aims: Considerable interest has been recently given to the potential role of the gut-brain axis (GBA) -a two-way communication network between the gut microbiota and the central nervous system- in the pathogenesis of attention-deficit hyperactivity disorder (ADHD), suggesting the potential usefulness of probiotic and synbiotic supplementations. In light of the limited available evidence, synbiotic efficacy in ADHD children not taking medications should be clarified. This study aimed to investigate the efficacy of a synbiotic dietary supplementation on fatty acids levels as well as on microbiota composition, behaviour, cognition, and brain function in children with ADHD.

View Article and Find Full Text PDF

Baicalein tethers CD274/PD-L1 for autophagic degradation to boost antitumor immunity.

Autophagy

December 2024

Institute of Energy Metabolism and Health, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

Immune checkpoint inhibitors, especially those targeting CD274/PD-L1yield powerful clinical therapeutic efficacy. Thoughmuch progress has been made in the development of antibody-basedCD274 drugs, chemical compounds applied for CD274degradation remain largely unavailable. Herein,baicalein, a monomer of traditional Chinese medicine, isscreened and validated to target CD274 and induces itsmacroautophagic/autophagic degradation.

View Article and Find Full Text PDF

Exploring the Role of Ccn3 in Type III Cell of Mice Taste Buds.

J Neurochem

January 2025

Department of Oral Physiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.

Different taste cells express unique cell-type markers, enabling researchers to distinguish them and study their functional differentiation. Using single-cell RNA-Seq of taste cells in mouse fungiform papillae, we found that Cellular Communication Network Factor 3 (Ccn3) was highly expressed in Type III taste cells but not in Type II taste cells. Ccn3 is a protein-coding gene involved in various biological processes, such as cell proliferation, angiogenesis, tumorigenesis, and wound healing.

View Article and Find Full Text PDF

The damaged organ may experience severe pathological alterations as a result of tissue ischemia-reperfusion (I/R). The study of stem cell-based repair therapies is actively being conducted, and the outcomes and therapeutic potential of these cells are both promising. Autophagy checks protein homeostasis by breaking down huge damaged proteins or organelles.

View Article and Find Full Text PDF

Background: It is unclear whether the extent of neuroaxonal damage, as measured by circulating levels of neurofilament light chain (NfL), would modify the effects of early antihypertensive therapy on cognitive performance following stroke. This study aimed to investigate the effects of early blood pressure reduction on the risk of post-stroke cognitive impairment (PSCI) among patients with different plasma NfL levels.

Methods: A total of 622 eligible patients from a pre-planned ancillary study of CATIS (China Antihypertensive Trial in Acute Ischemic Stroke) were included in this study.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!