Pairing of V_H gene families with the λ light chain: Evidence for a non‐stochastic association

Abstract

The frequencies at which four VH gene families pair with the lambda 1 light (L) chain were determined by sequential hybridization of VH- and lambda 1-specific DNA probes to mitogen-induced colonies of B cells. Analysis of pair frequencies indicates that the repertoire of lambda L chain antibodies is generated by the stochastic pairing of smaller 3'-to-mid-locus VH gene families (X-24, S107, Q52). However, the large 5' VH J558 family appeared to associate with the lambda 1 L chain non-stochastically; the frequency of VHJ558/lambda 1+ colonies among all lambda 1+ colonies was significantly lower than the frequency of J558 expression among all (C mu+) B cell colonies. This difference suggests that selection, either intrinsic at the level of rearrangement or heavy and L chain pairing, or extrinsic following surface immunoglobulin expression, may operate to shape the lambda antibody repertoire prior to the introduction of exogenous antigen.

The Primary Antibody Repertoire of κ‐Deficient Mice is Characterized by Non‐Stochastic Vλ1 + VH Gene Family Pairings and a Higher Degree of Self‐Reactivity

“…It has, however, been reported that the V l 2 gene is expressed predominantly in the peritoneal cavity and not in the spleen [8]. This is consistent with the fact that approximately 60% of the B-cell clones were positive for V l 1 expression, in agreement with previous observations [5,7,8]; this figure (60%) would have been expected to be higher had V l 2 transcripts been detected in significant numbers upon hybridization with BSC 1.5 DNA probe. It seems likely therefore that V l X þ V H gene family pairings contribute significantly to the splenic B-cell repertoire in the absence of k -light chain.…”

“…This is further supported by experiments with mice ᭧ 1998 Blackwell Science Ltd, Scandinavian Journal of Immunology, 48, 65-72 completely suppressed for k-light chain expression where 40-50% of splenic B-cell hybridomas and two-thirds of serum immunoglobulin expressed the l 1 -light chain [5]. Furthermore, a majority (42%) of B-cell clones from a population of l-enriched B lymphocytes from normal C57BL/6 mice were observed to express the Vl 1 gene [7]. Overall, these findings confirm that the Vl 1 gene is expressed in the majority of B lymphocytes with the l-light chain isotype.…”

“…Non-random V H gene expression and preferential V H þ V l associations have been observed in BALB/c mice immunized with anti-l-lipopolysaccharide (LPS) conjugates to activate l-secreting B-cell populations [11]. Another study revealed non-stochastic association of V H J558 þ V l 1 genes in a l-light chain enriched population of LPS-activated B cells from C57BL/6 mice [7]. Recently, predominant expression of the l 1 subtype has been observed in the spleen, lymph node and bone marrow of genetically manipulated mice, involving disruption of the C k gene resulting in a lack of the k-light chain, while l 2 and l 3 subtypes were expressed highly in the peritoneal B cells [8].…”

Analyses of Recombinant Stereotypic IGHV3-21–Encoded Antibodies Expressed in Chronic Lymphocytic Leukemia

“…Moreover, pre-B cells that express only IgH encoded by IGHV11-2 may not develop normally into immature B cells because of the poor association of such IgH with surrogate l L chain (10,11). Furthermore, the repertoire of mature B cells might be limited through a failure for certain IgH to pair with any but a few IgL (12)(13)(14)(15)(16)(17)(18). The most notable example of this is provided from studies on the repertoire of mouse B cells specific for phosphatidyl choline (PtC).…”

Analyse von B-lymphozytären Subpopulationen des darmassoziierten lymphatischen Gewebes

“…Eine weitere Erhöhung der Diversität wird durch die Kombination von schwerer und leichter Kette erreicht. Manche Kombinationen von IgH-und IgL-Ketten sind jedoch, wahrscheinlich aufgrund sterischer Hinderungen, ausgeschlossen (Yurovsky VV, 1993).…”