Depletion of conventional mature B cells and compromised specific antibody response in bovine immunoglobulin μ heavy-chain transgenic mice

In this study,we introduced the bovine immunoglobulinμheavy-chain gene(the orphaned gene on BTA11)into mouse germline cells.Bovine IgM was highly expressed in selected transgenic lines,and it largely inhibited rearrangements of the endogenous immunoglobulin heavy chain(IgH)genes in these lines.The forced expression of bovine IgM resulted in reduced numbers of pro-and pre-B cells but increased the number of immature B cells in the transgenic mice.Bovine IgM-expressing B cells can migrate from the bone marrow to the spleen,but most of the cells are arrested at the T1 transitional B cell stage,leading to a significantly lower number of T2 transitional and mature B cells in the spleen.Although the serum concentrations of endogenous IgM and IgG in the transgenic mice were significantly decreased,the IgA levels were slightly increased compared to the WT mice.The bovine IgM level in the serum was only one-tenth to one-fifth of that of endogenous mouse IgM,suggesting that most of the serum immunoglobulin were contributed by endogenous IgH gene-expressing B cells.These transgenic mice also exhibited a lower frequency of unique complementarity determining region 3(CDR3)sequences in their VH repertoire and Vκrepertoire but exhibited an increased frequency of unique CDR3 in their Vλrepertoire.Compared to the WT mice,the transgenic mice had a significantly higher percentage of mouse IgMexpressing B cells that expressedλchains.Finally,we showed that the transgenic mice were deficient in a specific antibody response to antigen stimulation.