Selection of stereotyped VH81X-{micro}H chains via pre-B cell receptor early in ontogeny and their conservation in adults by marginal zone B cells.
The pre-B cell receptor (preBCR) plays critical roles in early B cell differentiation. It has been shown that not all muH chains are capable of pairing with surrogate light (SL) chains to form preBCR. Here, we established a novel system to differentially identify two types of early pre-B cell populations in bone marrow and fetal liver of mice, one producing SL-pairing muH chains and the other producing SL-non-pairing muH chains. The former population accounted for 80% of all the early pre-B cells in adult bone marrow, while it accounted for only 20% of those in fetal liver. Comparison of the two types of pre-B cell populations in fetal liver revealed the structural difference between SL-pairing and -non-pairing muH chains encoded by the V(H)81X segment that was most frequently utilized in fetal liver pre-B cells but rarely expressed by B cells generated in adults. PreBCR played an important role in the positive selection of V(H)81X-muH chains carrying the characteristic sequences of the complementarity-determining region 3 with little or no nibbling or N nucleotide addition, leading to their predominance in neonatal splenic B cells. These fetal-type V(H)81X-muH chains were also detected in adult spleen, but almost exclusively in marginal zone (MZ) B cells in contrast to the adult-type V(H)81X-muH chains. This strongly suggests that neonatally generated and selected B cells expressing the stereotyped V(H)81X-muH chains are maintained in the adult MZ and could function as innate-like lymphocytes.
Kawano
Yohei
Y
Department of Immune Regulation, Tokyo Medical and Dental University Graduate School, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Yoshikawa
Soichiro
S
Minegishi
Yoshiyuki
Y
Karasuyama
Hajime
H
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology; D022801:Complementarity Determining Regions / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain / Q000276:immunology*; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain / Q000276:immunology; D007148:Immunoglobulin mu-Chains / Q000276:immunology*; D008099:Liver / Q000254:growth & development / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D054420:Pre-B Cell Receptors; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000254:growth & development / Q000276:immunology
D022801:Complementarity Determining Regions; D007148:Immunoglobulin mu-Chains; D008562:Membrane Glycoproteins; D054420:Pre-B Cell Receptors; D011947:Receptors, Antigen, B-Cell