Pre-B and B cells in rabbits. Ontogeny and allelic exclusion of kappa light chain genes.

Abstract

Mononuclear cells containing small amounts of cytoplasmic IgM (clgM+) a but lacking stable surface immunoglobulin (sIg) appear in both mouse and human fetal liver before the earliest sIg + B lymphocytes (1-3). These eIgM+'sIg -cells, called pre-B cells, are the least mature members of the B-cell lineage so far identified in mammals. Well defined allotypic markers on the kappa light chains of rabbit immunoglobulins Co-allotypes) provide a means for the further analysis of pre-B and B-cell development (4). The expression of immunoglobulin molecules by rabbit B cells is controlled by regulatory and/or structural genes for the variable and constant regions of heavy, kappa, and lambda chains occurring as separate clusters at three unlinked, complex loci. The particular immunoglobulin polypeptide chains synthesized by each cell result from the activation of selected members of the linked gene clusters. In heterozygous rabbits, individual plasma cells synthesize Ig of only one of the alternative allotypes (5-6), apparently using genes inherited from one parent but not both. The mechanism of this allelic exclusion has not been established and the stage of B-cell differentiation at which it occurs is uncertain because of the conflicting results of tests for allotype exclusion by B lymphocytes.When blood lymphocytes from b4b 5 rabbits were treated with 125I anti-b4 and antib5 (7), or studied by combined immunofluorescence and radioautography (8), the majority of B lymphocytes had only one sIg allotype detectable but a small percentage *

B Lymphocyte Development in Rabbit: Progenitor B Cells and Waning of B Lymphopoiesis

“…In contrast to mice, in which preB cells are found in bone marrow throughout life, in rabbits the number of preB cells is highest around birth (22) or at 2-3 wk of age (5) and then steadily decreases until they are undetectable in adults (5). To confirm these data, Crane et al (6) examined levels of B cell recombination excision circles (BRECs) in bone marrow of young and adult rabbits.…”

“…In addition, a small percentage of B cells in mice develop through an alternative preBCR-independent pathway in which the L chain rearranges independently of the H chain (17)(18)(19)(20)(21). In rabbits, the only progenitor B cells described are preB cells, which have been identified in fetal liver, fetal spleen, and neonatal bone marrow (5,22,23). The presence of a -chain and the absence of the L chain in virtually all preB cells suggests that B cell development in rabbit likely occurs through the classical, or ordered, pathway, mediated by a preBCR.…”

A Life of Adventure in Immunobiology

“…This distinguishing feature of pre-B cells allowed us to show in subsequent experiments that large pre-B cells undergo proliferation before giving rise to small resting pre-B cells that in turn differentiate to become B cells, the immaturity of which makes them exquisitely vulnerable to receptor cross-linkage (55). The elucidation of this sequence of events provided a useful model of early B cell differentiation and the means to demonstrate B cell generation in hematopoietic tissues of other mammalian species, including humans and rabbits (56)(57)(58). We originally thought pre-B cells made both heavy and light chains, but studies of pre-B cell hybridomas convincingly showed that they only produce μ heavy chains (59).…”

B Lymphocyte Development in the Rabbit

“…Pre-B cells first appear in the fetal bone marrow at day 25 of gestation (Hayward et al, 1978;McElroy et al, 1981), and increase in number after birth. Peak levels of pre-B cells representing from 9% to 19% of total nucleated cells, are found in the bone marrow between birth and 2 weeks of age (Hayward et al, 1978;McElroy et al, 1981;Gathings et al, 1981;. The number rapidly decreases soon after birth, until in adult bone marrow, pre-B cells account for only 1-3% of total nucleated cells (Gathings et al, 1981).…”

“…However, several groups have identified pre-B cells in the rabbit on the basis of a ClsIg-phenotype. Using this criterion, Hayward et al (1978) andMcElroy et al (1981) identified pre-B cells in the fetal liver beginning at days 17-19. Levels of pre-B cells in the liver appear to peak at birth and are almost undetectable by day 10 postnatally.…”