Selection of stereotyped V_H81X-μH 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 μH 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 μH chains and the other producing SL-non-pairing μH 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 μH chains encoded by the V_H81X 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_H81X-μH 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_H81X-μH chains were also detected in adult spleen, but almost exclusively in marginal zone (MZ) B cells in contrast to the adult-type V_H81X-μH chains. This strongly suggests that neonatally generated and selected B cells expressing the stereotyped V_H81X-μH chains are maintained in the adult MZ and could function as innate-like lymphocytes.