Combinatorial immunoglobulin light chain variability creates sufficient B cell diversity to mount protective antibody responses against pathogen infections

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Abstract
To analyze how combinatorial light (L) chain diversity influences the B cell repertoire, we studied mice with a homozygous immunoglobulin‐heavy‐chain null mutation (μMT), in which the B cell developmental block was overridden by the expression of a transgenic immunoglobulin μ heavy (H) chain derived from a vesicular stomatitis virus Indiana serotype (VSV‐IND)‐neutralizing Ab (T11μMT mice). The randomly integrated transgene could not undergo secondary rearrangements and was expressed in combination with endogenous κ or λ chains. T11μMT mice had a skewed B cell repertoire as evidenced by 30–60% VSV‐IND‐specific peripheral B cells and spontaneous VSV‐IND‐neutralizing serum titers. Upon immunization, T11μMT mice mounted specific IgM antibody responses against VSV‐IND but, interestingly, they also responded against VSV New Jersey serotype (VSV‐NJ), lymphocytic choriomeningitis virus, poliovirus and Salmonella typhi porins. Variable‐region sequence analysis revealed that VSV‐NJ‐specific antibodies expressed numerous L chains in combination with the transgenic H chain, which was devoid of hypermutations. Thus, in T11μMT mice combinatorial L chain variability alone is able to build up a sufficiently complex B cell repertoire to mount protective immunoglobulin responses against a variety of pathogens.