The Ig heavy (H) chain plays a pivotal role in the regulation of primary B cell development through its association with a variety of other proteins including Igα and Igβ, the surrogate light chain components and bona fide L chains, to form transmembrane signaling complexes. Little is known about how alterations in the structure of the H chain variable region influence association with these proteins, or the signaling capacity of the complexes that form. Here we describe a line of VH "knockin" mice in which the transgene-encoded VH region differs by eight amino acid residues from the VH region in a VH knockin line we previously constructed and characterized. The transgenic H chain locus in the line of mice we characterized earlier efficiently promotes H chain allelic exclusion and all phases of primary B cell development, resulting in the generation of mature B1, marginal zone (MZ) and follicular (FO) B cell compartments. In contrast, the transgenic H chain locus in the new line fails to enforce allelic exclusion, as evidenced by the majority of peripheral B cells expressing two H chains on their surfaces. Moreover, this locus inefficiently drives bone marrow B lymphopoiesis and FO B cell development. However, this H chain locus does promote MZ B cell development, from precursors that appear to be generated during fetal and neonatal life. We discuss these data in the context of previous findings on the influence of Ig H chain structure on primary B cell development.
Bibliographical noteFunding Information:
We thank Randy Hardy for the JHD mice and for conducting some pilot flow cytometry studies, Larry Wysocki and Katja Aviszus for the Vκ1060 mice and Kerstin Kiefer for a review of the manuscript. Technical support was provided by the Flow Cytometry and Transgenic/Knockout Facilities of the Kimmel Cancer Center. We also thank Scot Fenn for technical help and all members of the Manser laboratory for their indirect contributions to this work. This studies was funded by research grants from the National Institutes of Health (NIH; AI23739 and AI38965) to T.M., and an NIH training grant (CA72318) supported L.H.
- Antibody heavy chain
- B cells
- Transgenic mice