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LETTERS TO THE EDITOR |
Hôpital Cochin, Paris, France
Schuh and colleagues (1) recently reported that a transgenic Sp6-µHC can be transported to the cell surface in the absence of surrogate and conventional light chains (rag-deficient background). They ascribe this property to the Sp6-variable region, and speculate that the production of some µ chains with particular variable regions could explain the "leaky" phenotype of 
5-deficient mice. We have found that a transgenic Sp6-human µ heavy chain was inefficient in correcting pre-B cell development in rag-proficient, 5-deficient mice, while a V-less human µ chain relieved the requirement for surrogate light chains (2). Our data suggest that there is nothing particular with the Sp6 variable region and that the good efficiency in promoting pre-B cell development in the rag-deficient background might be related to homeostatic compensation due to Ig and B cell deficiency. Another interpretation of their data, that we favor, is that any rearranged µ gene can give rise to a minority of VDJ-less transcripts by splicing of the leader exon to the CH1 exon, which, in mouse as in man, can induce V-less protein production (3, 4). This is consistent with the low expression of µ chain on the surface. In the transgenic model described by Schuh and colleagues, the presence or the absence of variable region on the B cell surface should be tested.
References
5: a paradigm revisited. J. Immunol. 171:3343.-5 in transgenic mice expressing a heavy-chain disease protein. Curr. Biol. 5:1140.[Medline]
Division of Molecular Immunology, Department of Internal Medicine III, Nikolaus-Fiebiger Center, University of Erlangen, Erlangen, Germany
In his comments about our manuscript entitled "Cutting Edge: Signaling and Cell Surface Expression of a µH Chain (µHC) in the Absence of 5: A Paradigm Revisited" (R1 ), Corcos argues that the positive effect of the transgenic Sp6-µHC on the progression of cells from the pro-B to the pre-B cell stage in the absence of 5 might rather be the result of signals delivered by a truncated µHC lacking the VH region (V-less µHC) than by the wild-type Sp6-µHC.
The idea that truncated VH-less µHCs promote the transition of cells from the pro-B to the pre-B stage even in the absence of a complete surrogate light chain (SLC) has been verified in transgenic mouse models by Corcos and coworkers (R2 ) as well as Schlissel and coworkers (R3 ). However, in our system we can exclude the presence of truncated VH-less µHCs, since, as already published in an earlier manuscript by Hess et al. (see Fig. 2D in Ref. R4 ), we detected in bone marrow B-lymphoid cells by Western blot analysis only a signal corresponding to a 70-kDa full-length µHC but never a signal indicating the presence of a shorter chain. Therefore, developmental progression of pro-B cells in the absence of 5 is driven in our transgenic mouse model by a full-length wild-type Sp6-µHC rather than a VH-less µHC.
In his comments, Corcos also mentioned that a chimeric µHC composed of the mouse VHSp6 region and the human Cµ region (chimeric mouse/human Sp6-µHC) was inefficient in promoting pre-B cell development in 5-deficient, Rag-proficient mice (R2 ). This statement is somewhat misleading, since the contour blots in Fig. 4 in Ref. R2 clearly show that the chimeric mouse/human Sp6-µHC supports the progression of pro-B cells into CD43-negative pre-B cells in transgenic 5-deficient mice when compared with nontransgenic 5-deficient mice, albeit with a lower efficiency than in 5-proficient transgenic mice. Therefore, the findings by Corcos et al. (R2 ) are in line with our findings and support the conclusion that a full-length Sp6-µHC promotes progression of pro-B cells in the absence of a 5 chain, although with a lower frequency than in the presence of 5.
We also think that the positive effect of a transgenic Sp6-µHC on pro-B cell progression in the absence of 5 is due to a structural feature of the VHSp6 region, since Nussenzweig and coworkers found that a chimeric mouse/human µHC using another murine VH region (i.e., VH3–38; Ref. R5 ) does not support the progression of pro-B cells in a transgenic 3-38-µHC, 5/Rag-double-deficient mouse (R6 ).
In summary, our findings (R1 ) as well as that of Corcos et al. (R2 ) and Nussenzweig et al. (R6 ), strongly support the idea that the leaky phenotype of B cell maturation in 5-deficient mice could be explained by the production of some µHCs that gain in a VH-dependent manner surface transport-and signaling competency even in the absence of a complete SLC.
References
5: a paradigm revisited. J. Immunol. 171:3343.
-5 in transgenic mice expressing a heavy-chain disease protein. Curr. Biol. 5:1140.
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