Although a variety of novel strategies have been used to select antibody-producing cells efficiently either from natural B cell collections or from plasma cell collections postimmunization, the production of monoclonal antibodies against weak antigens with high affinity and special epitopes for diagnostic or therapeutic applications remains fraught with challenges and uncertainty. In this report, we proposed an effective method for generating monoclonal antibodies from rabbits by using histone deacetylase inhibitor (HDACi) to improve antibody gene diversity, particularly the diversity of the complementarity-determining regions (CDRs) which determines the specificity of the antibody. HDACi was encapsulated in nanoliposomes to form an immunomodulator, which was administered to neonatal rabbits during the ontogeny of the immune systems. It was observed that the number of antigen-specific plasma cells in these treated rabbits was increased, and more importantly, the antibody gene diversity, especially the CDRs, was proven to have increased after 3 times of antigen immunization compared with the untreated group, probably due to the promoted efficiency of gene conversion. The results indicated that the histone modification mediated by HDACi treatment has an effect of promoting diversification of the antibody genes in treated animals. The nanoliposomes as a carrier of HDACi helped to increase the utilization rate of the loaded drugs, reduce the total dosage of administrations, and extend the time interval between administrations, making the drug feasible for newborn animals. This new method enables animals to generate antibodies against different epitopes of weakly immunogenic antigens, such as peptide antigens, and makes it possible to select antibodies with better performance for subsequent application in diagnostic reagents.
Chen et al. (2026) studied this question.