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Selection at multiple checkpoints focuses V(H)12 B cell differentiation toward a single B-1 cell specificity.

Tatu C, Ye J, Arnold LW, Clarke SH - J. Exp. Med. (1999)

Bottom Line: In 6-1 mice, splenic B-1 cells reside in follicles but segregate to follicles distinct from those that contain B-2 cells.These data indicate that selection at multiple developmental checkpoints ensures the co-expression of an anti-PtC V(H)CDR3 and L chain in a high frequency of V(H)12 B cells.This focus toward specificity for PtC facilitates the development of a large anti-PtC B-1 repertoire.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.

ABSTRACT
Phosphatidyl choline (PtC)-specific B cells segregate to the B-1 subset, where they comprise up to 10% of the B-1 repertoire. About half express V(H)12 and Vkappa4/5H and are restricted in V(H)CDR3. We have previously reported that anti-PtC V(H)CDR3 is enriched among V(H)12-expressing cells by selective elimination of pre-B cells. We report here a bias for Vkappa4/5H expression among V(H)12-expressing B cells, even among those that do not bind PtC and are not B-1. This is due in part to an inability of V(H)12 to associate with many light (L) chains but must also be due to a selective advantage in survival or clonal expansion in the periphery for Vkappa4/5H-expressing cells. Thus, the bias for Vkappa4/5H expression is independent of PtC binding, and, as segregation to B-1 occurs after Ig gene expression, it precedes segregation to the B-1 subset. In 6-1 mice, splenic B-1 cells reside in follicles but segregate to follicles distinct from those that contain B-2 cells. These data indicate that selection at multiple developmental checkpoints ensures the co-expression of an anti-PtC V(H)CDR3 and L chain in a high frequency of V(H)12 B cells. This focus toward specificity for PtC facilitates the development of a large anti-PtC B-1 repertoire.

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Jκ use by 6-1 and non-Tg littermate mice. (A) Jκ use by Vκ4/5H rearrangements from the PtCneg, PtCint, and PtCbri populations of 6-1 mice. (B) Jκ use by non-Vκ4/5 rearrangements from the PtCneg population of 6-1 mice. (C) Jκ use by B-0 (CD23+B220+) cells of non-Tg littermates. The total numbers of sequences analyzed in each group are given in Fig. 2 and Fig. 3.
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Figure 4: Jκ use by 6-1 and non-Tg littermate mice. (A) Jκ use by Vκ4/5H rearrangements from the PtCneg, PtCint, and PtCbri populations of 6-1 mice. (B) Jκ use by non-Vκ4/5 rearrangements from the PtCneg population of 6-1 mice. (C) Jκ use by B-0 (CD23+B220+) cells of non-Tg littermates. The total numbers of sequences analyzed in each group are given in Fig. 2 and Fig. 3.

Mentions: These three populations of B cells in 6-1 mice are distinct in Jκ use. The PtCbri B-1 cells use predominantly Jκ2 and Jκ4 (Fig. 4 A), as is true of PtC-specific lymphomas and hybridomas 19. This bias undoubtedly reflects selection for this specificity and expansion in the B-1 subset. PtCint B-0 cells use Jκ2 almost exclusively. We attribute this to the fact that a tyrosine at the Vκ–Jκ junction, which is encoded by Jκ2, results in PtCint binding. Vκ4/5H-expressing PtCneg B-0 cells use Jκ2, -4, and -5, with Jκ5 used at almost twice the frequency as Jκ2 (Fig. 4 A). Notably, almost none of the Vκ4/5H-expressing B cells from any of these populations use Jκ1. This contrasts with the predominant use of Jκ1 and Jκ2 by non-Tg B-0 cells (Fig. 4 C) and even by non-Vκ4/5 genes from the PtCneg B-0 cells (Fig. 4 B).


Selection at multiple checkpoints focuses V(H)12 B cell differentiation toward a single B-1 cell specificity.

Tatu C, Ye J, Arnold LW, Clarke SH - J. Exp. Med. (1999)

Jκ use by 6-1 and non-Tg littermate mice. (A) Jκ use by Vκ4/5H rearrangements from the PtCneg, PtCint, and PtCbri populations of 6-1 mice. (B) Jκ use by non-Vκ4/5 rearrangements from the PtCneg population of 6-1 mice. (C) Jκ use by B-0 (CD23+B220+) cells of non-Tg littermates. The total numbers of sequences analyzed in each group are given in Fig. 2 and Fig. 3.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2195649&req=5

Figure 4: Jκ use by 6-1 and non-Tg littermate mice. (A) Jκ use by Vκ4/5H rearrangements from the PtCneg, PtCint, and PtCbri populations of 6-1 mice. (B) Jκ use by non-Vκ4/5 rearrangements from the PtCneg population of 6-1 mice. (C) Jκ use by B-0 (CD23+B220+) cells of non-Tg littermates. The total numbers of sequences analyzed in each group are given in Fig. 2 and Fig. 3.
Mentions: These three populations of B cells in 6-1 mice are distinct in Jκ use. The PtCbri B-1 cells use predominantly Jκ2 and Jκ4 (Fig. 4 A), as is true of PtC-specific lymphomas and hybridomas 19. This bias undoubtedly reflects selection for this specificity and expansion in the B-1 subset. PtCint B-0 cells use Jκ2 almost exclusively. We attribute this to the fact that a tyrosine at the Vκ–Jκ junction, which is encoded by Jκ2, results in PtCint binding. Vκ4/5H-expressing PtCneg B-0 cells use Jκ2, -4, and -5, with Jκ5 used at almost twice the frequency as Jκ2 (Fig. 4 A). Notably, almost none of the Vκ4/5H-expressing B cells from any of these populations use Jκ1. This contrasts with the predominant use of Jκ1 and Jκ2 by non-Tg B-0 cells (Fig. 4 C) and even by non-Vκ4/5 genes from the PtCneg B-0 cells (Fig. 4 B).

Bottom Line: In 6-1 mice, splenic B-1 cells reside in follicles but segregate to follicles distinct from those that contain B-2 cells.These data indicate that selection at multiple developmental checkpoints ensures the co-expression of an anti-PtC V(H)CDR3 and L chain in a high frequency of V(H)12 B cells.This focus toward specificity for PtC facilitates the development of a large anti-PtC B-1 repertoire.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.

ABSTRACT
Phosphatidyl choline (PtC)-specific B cells segregate to the B-1 subset, where they comprise up to 10% of the B-1 repertoire. About half express V(H)12 and Vkappa4/5H and are restricted in V(H)CDR3. We have previously reported that anti-PtC V(H)CDR3 is enriched among V(H)12-expressing cells by selective elimination of pre-B cells. We report here a bias for Vkappa4/5H expression among V(H)12-expressing B cells, even among those that do not bind PtC and are not B-1. This is due in part to an inability of V(H)12 to associate with many light (L) chains but must also be due to a selective advantage in survival or clonal expansion in the periphery for Vkappa4/5H-expressing cells. Thus, the bias for Vkappa4/5H expression is independent of PtC binding, and, as segregation to B-1 occurs after Ig gene expression, it precedes segregation to the B-1 subset. In 6-1 mice, splenic B-1 cells reside in follicles but segregate to follicles distinct from those that contain B-2 cells. These data indicate that selection at multiple developmental checkpoints ensures the co-expression of an anti-PtC V(H)CDR3 and L chain in a high frequency of V(H)12 B cells. This focus toward specificity for PtC facilitates the development of a large anti-PtC B-1 repertoire.

Show MeSH
Related in: MedlinePlus