Immunoglobulin gene rearrangement in B cell deficient mice generated by targeted deletion of the J_H locus

Abstract

B lymphocyte differentiation is characterized by an ordered series of Ig gene assembly and expression events. In the majority of normal B cells, assembly and expression of Ig heavy (H) chain genes precedes that of light (L) chain genes. To determine the role of the Ig heavy chain protein in B cell development and L chain gene rearrangement, we have generated mice that cannot assemble Ig H chain genes as a result of targeted deletion of the JH gene segments in embryonic stem cells. Mice homozygous for this deletion are devoid of slg+ B cells in the bone marrow and periphery. B cell differentiation in these mice is blocked at the large, CD43+ precursor stage. However, these precursor B cells do assemble kappa L chain genes at a low level in the absence of mu H chain proteins. These data demonstrate that rearrangement and expression of the mu H chain gene is not absolutely required for kappa L chain gene rearrangement in vivo. Expression of mu chains may facilitate either efficient L chain gene rearrangement or the survival of cells that have rearranged light chain genes by promoting the differentiation of large, CD43+ to small, CD43- pre-B cells.

Cutting Edge: Transplant Tolerance Induced by Anti-CD45RB Requires B Lymphocytes

“…To confirm the generality of this finding, we extended this analysis to the TS1 transgenic model and developed a line of B cell-deficient TS1 mice (BALB/c background) by interbreeding our TS1 mice with the BALB/c Jh Ϫ/Ϫ line (19). The Jh Ϫ/Ϫ line does not develop mature B cells or produce Ab.…”

B cells are required for Aire-deficient mice to develop multi-organ autoinflammation: A therapeutic approach for APECED patients

“…Therefore, we crossed AireϪ/Ϫ animals with another line having a more robust block in B cell differentiation. JhϪ/Ϫ mice lack the junctional region of the immunoglobulin (Ig) heavy chain and are thereby incapable of assembling a surface B-cell receptor, leading to a block in B-cell maturation at the pro-B to pre-B-transition (18). We analyzed autoimmunity in AireϪ/ϪJhϪ/Ϫ double-knockout mice, this time on the BALB/c background, compared with AireϪ/Ϫ littermate controls.…”

Antigen Receptor Editing in Anti-DNA Transitional B Cells Deficient for Surface IgM

“…Investigators interested in obtaining mice homozygous for the tgs reported here should contact the Mutant Mouse Regional Resource Center (www.mmrrc.org). All of the mice used in this study, including BALB/c scid/ scid (SCID mice), C57BL/6, (C57BL/6 ϫ BALB/c)F 1 mice, and C.B-17 mice with deleted JH loci (JH Ϫ/Ϫ mice) (25), were raised and maintained behind a barrier as specific pathogen-free mice in the Laboratory Animal Facility of the Fox Chase Cancer Center. Mice were used between 8 and 12 wk of age (unless otherwise stated) according to the protocols approved by the Animal Care and Use Committee of this institution.…”