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International Immunology, Vol. 12, No. 3, 385-395, March 2000
© 2000 Japanese Society for Immunology

Affiliation to mature B cell repertoire and positive selection can be separated in two distinct processes

Soulef Hachemi-Rachedi1, Anne-Marie Drapier1, Pierre-André Cazenave1 and Pierre Sanchez1,2

1 Immunochimie Analytique, Institut Pasteur and
2 Immunobiologie, Université Denis Diderot, 75251 Paris, France

Correspondence to: P. Sanchez, Laboratoire d'Immunobiologie Case 7048, Université Denis Diderot (PARIS VII), 2 Place Jussieu, 75251 Paris Cedex 05, France

Using an `oligoclonal' model, we have previously shown that mice transgenic for a µ chain (H3) and deficient for {kappa} chain expression display a mature B cell repertoire largely dominated by the H3/{lambda}1 pair, while the four H3/{lambda} available combinations can be observed in the immature B cell compartment. This led us to propose the existence of a positive selection process. To test this hypothesis, we have introduced the SJL {lambda} locus coding for a defective {lambda}1 chain ({lambda}1s) that creates a dysfunctional Ig receptor complex during B cell differentiation. Our results show that the {lambda}1s defect impairs the development of mature B cells when the H3-µ transgene insert is present in the hemizygous state. This suggests that the Gly -> Val substitution present in the C{lambda}1s chain at position 155 is sufficient to abrogate the selection of the H3/{lambda}1 pair. Unexpectedly, when the H3-µ transgene array is present in a homozygous state in {lambda}1s mice but not in `wild-type' {lambda}1 mice ({lambda}1+), a significant number of mature B cells expressing all H3/{lambda} combinations can be developed. These results indicate that the overriding H3/{lambda}1 dominance observed in {lambda}1+ mice is due to a positive selection process and not to a negative selection of other H3/{lambda} combinations. They also show that the export of B cells to the periphery can be controlled by the expression of the µ chain.

Keywords: B lymphocytes, cellular differentiation, repertoire development, transgenic/knockout

Transmitting editor: J. F. Kearney


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