We have examined the amino-terminal sequence of the Kc light chains of a set of monoclonal antibodies specific for one of the major antigenic determinants (Sb) on the influenza virus PR8[A/PR/8/34(HlNl)J hemagglutinin molecule. This set was believed to be structurally related from earlier serological analysis that typed these K chains as members of the variable (V) region VK21 group [Staudt, L. M. & Gerhard, W. (1983) J. Exp. Med. 157,. Our sequence analysis confirms and extends this conclusion; all examples of this set belong to a subgroup of the VK21 group, V,,21C. A special feature of this set of K light chains is that all examples were derived from the same mouse (designated H36). This sequence analysis along with the characterization of gene rearrangements at the K light chain loci of these hybridomas is consistent with the idea that certain members of this set are the progeny of one or two lymphocytes. Because of this potential clonal relationship, we can reach several conclusions about the diversity observed among these K light chains: (') the diversity is due to somatic mutation, (it) somatic mutations occur sequentially and accumulate in the first complementarity-determining region, and (iii) the extent of somatic variation in this sample is high, suggesting a somatic mutation rate of about 10-3 per base pair per generation.Antibody diversity arises from several sources. Individuals inherit multiple variable (V) region gene segments for both heavy (VH) and light (VK, VA) chains, joining (J) gene segments (JH, J,, Jh), and diversity (D) gene segments (DH).The initial antibody repertoire of an individual is a product of the combinatorial joining of these gene segments, i.e., V4s with JKS or different VH, DH, and JH combinations, that form complete V1 or VH genes. Errors committed during the process of joining contribute additional diversity to this repertoire (reviewed in ref. 1). Finally, that somatic mutation further amplifies this germ-line repertoire seems to be established (2). The original evidence for somatic mutation favored a model by which point mutations accumulate sequentially during cell division (3). Other models link somatic mutation with specific events during lymphocyte differentiation (4, 5) and propose cataclysmic mechanisms of mutagenesis that introduce multiple amino acid substitutions in one step (6, 7). These models are based on the comparison of V region sequences of independently induced plasmacytoma and hybridoma antibodies to their putative germ-line counterparts. Hence, little can be concluded about the time course of somatic mutation.A better understanding of the nature of somatic mutation can be reached by comparisons of the V genes of a cell lineage. Scharff and colleague have analyzed certain mutants and revertants of the cell line S107 and conclude that the in vitro rate of mutation at the VH gene expressed in this plasmacytoma is significantly higher than that of nonimmunoglobulin genes (8). A possible in vivo analogy is described here: we have initiated a structu...
In the retina of herring (Clupea harengus L.), rods are recruited from about 8 wk after hatching, and from this time there is a linear relationship between the number of rods in the photoreceptor cell population and the content of di22:6n-3 molecular species of phospholipids. Juvenile herring were reared from four weeks' post-hatching for 15 wk on either Artemia nauplii deficient in 22:6n-3 or on enriched Artemia nauplii containing 4.3% 22:6n-3. The visual performance of the fish was then determined at three light intensities (0.01, 0.1, and 1.0 lux) by observing their frequency of striking at live Artemia nauplii using infrared video recording. Herring reared on the diet containing no 22:6n-3 were less active predators, especially at the lowest light intensity where very few strikes were observed. The eyes of these fish contained greatly reduced levels of di22:6n-3 molecular species of total phospholipid, 2.1% vs. 12.0% in fish supplemented with 22:6n-3. The contribution of saturated and monounsaturated fatty acids in the molecular species of phosphatidylethanolamine (PE), phosphatidylserine (PS), and phosphatidylcholine (PC) was virtually unchanged, while 20:5n-3 and 22:5n-3 largely replaced 22:6n-3. There was an almost complete disappearance of di22:6n-3 PC, while the amounts of di22:6n-3 PE and PS fell by 18.1 and 20.6% to 2.7 and 7.6%, respectively. The dipolyunsaturated molecular species di20:5n-3, 20:5n-3/22:5n-3, and di22:5n-3 made up a substantial part of the deficit. We conclude that a dietary deficiency of 22:6n-3 during the period early in rod development impairs visual performance such that the fish can no longer feed at low light intensities.
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