The initiation of B cell clonal expansion occurs independently of pre-B cell receptor formation.
Current models of B cell development posit that clonal expansion occurs as a direct result of Ig H chain expression. To test this hypothesis, we isolated a population of early B cells in which H chain recombination is initiated and assessed V(H)DJ(H) rearrangements in both cycling and noncycling cells. We found that actively dividing cells within this population are enriched for H chain rearrangements that are productive when compared with their counterparts in G(0)/G(1), apparently supporting a role for H chain expression in initiating early B cell division; entrance into the cell cycle was accompanied by V(H) gene-dependent H chain selection. However, we also identified a phenotypically identical population of actively cycling early B cells in the absence of H chain expression in recombination activating gene knockout mice. In addition, actively cycling early B cells could be detected in pre-B cell receptor (pBCR)-negative lambda5 knockout mice, but we found no evidence for V(H)-dependent H chain selection in this population. Given these results, we suggest that the initiation of clonal expansion, at this early stage in B cell development, occurs independently of H chain expression. Although the cycling cell pool is enriched for pBCR-positive cells in mice expressing surrogate L chain, pBCR formation is not required for the initiation of cell division.
Kline
G H
GH
Basel Institute for Immunology, Basel, Switzerland. kline@bii.ch
Hayden
T A
TA
Riegert
P
P
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D015321:Gene Rearrangement; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011498:Protein Precursors / Q000096:biosynthesis*; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis*; D011995:Recombination, Genetic / Q000235:genetics
D007143:Immunoglobulin Heavy Chains; D011498:Protein Precursors; D011947:Receptors, Antigen, B-Cell