B lymphocyte deficiency in IgH-transgenic rabbits.
We developed IgH-transgenic rabbits carrying a productive VDJ-Cmu Tg and found the rabbits were B cell-deficient, with a 50-100% reduction in serum IgM and IgG levels. The bone marrow of newborn Tg rabbits contained severely reduced levels of preB cells and almost no B cells. The few preB cells present in the bone marrow were large, cycling cells that expressed the VDJ-Cmu Tg, indicating that the block in B cell development likely occurred at or before the transition from large (early) preB to small (late) preB cells. By immunoprecipitation, the Tg mu-chain paired with VpreB and lambda5, suggesting that the B cell deficiency is not due to an inability to form a preB cell receptor. Despite the block in B cell development, a few B cells, expressing predominantly endogenous mu-chains, began the second stage of development in GALT. B cells were localized in and beneath the follicle-associated epithelium of GALT prior to B cell follicle formation, suggesting to us that B cell follicle formation is initiated near the follicle-associated epithelium, possibly through contact with intestinal microbiota. These IgH-Tg rabbits should provide a useful model for studies of B cell development both in bone marrow and in GALT.
Jasper
Paul J
PJ
Department of Microbiology and Immunology, Loyola University Chicago, Maywood, IL 60153, USA.
Rhee
Ki-Jong
KJ
Kalis
Susan L
SL
Sethupathi
Periannan
P
Yam
Pi-Chen
PC
Zhai
Shi-Kang
SK
Knight
Katherine L
KL
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D050438:Genes, Immunoglobulin Heavy Chain; D018928:Immunity, Mucosal; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007148:Immunoglobulin mu-Chains / Q000235:genetics; D007150:Immunohistochemistry; D007422:Intestines / Q000276:immunology*; D011817:Rabbits / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050441:VDJ Exons
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007148:Immunoglobulin mu-Chains