Antigen-binding repertoire and Ig H chain gene usage among B cell hybridomas from normal and autoimmune mice.

Striebich, Christopher C.; Miceli, Robert M.; Schulze, Dan H.; Kelsoe, Garnett; Černý, Jan

doi:10.4049/jimmunol.144.5.1857

Cited by 25 publications

(1 citation statement)

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“…Because naive lymphocytes do not run the risk of inducing inappropriate responses, it might be beneficial to have naive cells that are more cross-reactive than the memory cells. Interestingly, naive B cells indeed appeared to react to a broader range of Ags than did memory B cells (51) (see also Ref. 52 and references therein).…”

Section: Discussionmentioning

confidence: 93%

How Specific Should Immunological Memory Be?

Borghans

Noest

Boer

1999

The Journal of Immunology

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Protection against infection hinges on a close interplay between the innate immune system and the adaptive immune system. Depending on the type and context of a pathogen, the innate system instructs the adaptive immune system to induce an appropriate immune response. Here, we hypothesize that the adaptive immune system stores these instructions by changing from a naive to an appropriate memory phenotype. In a secondary immune reaction, memory lymphocytes adhere to their instructed phenotype. Because cross-reactions with unrelated Ags can be detrimental, such a qualitative form of memory requires a sufficient degree of specificity of the adaptive immune system. For example, lymphocytes instructed to clear a particular pathogen may cause autoimmunity when cross-reacting with ignored self molecules. Alternatively, memory cells may induce an immune response of the wrong mode when cross-reacting with subsequent pathogens. To maximize the likelihood of responding to a wide variety of pathogens, it is also required that the immune system be sufficiently cross-reactive. By means of a probabilistic model, we show that these conflicting requirements are met optimally by a highly specific memory lymphocyte repertoire. This explains why the lymphocyte system that was built on a preserved functional innate immune system has such a high degree of specificity. Our analysis suggests that 1) memory lymphocytes should be more specific than naive lymphocytes and 2) species with small lymphocyte repertoires should be more vulnerable to both infection and autoimmune diseases.

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Section: Discussionmentioning

confidence: 93%

How Specific Should Immunological Memory Be?

Borghans

Noest

Boer

1999

The Journal of Immunology

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Posttranslational protein modifications, apoptosis, and the bypass of tolerance to autoantigens

Utz

Anderson

1998

Arthritis & Rheumatism

191

135

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Correlation of antibody multireactivity with variable region primary structure among murine anti‐erythrocyte autoantibodies

Conger¹,

Sage²,

Corley³

1992

Eur J Immunol

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A high proportion of the antibodies in the preimmune repertoire bind to several unrelated antigens and are considered to be multireactive. This property is reportedly associated with the antibodies produced by CD5+ B lymphocytes. Because many antibodies specific for bromelain-treated mouse red blood cells (BrMRBC) derive from CD5+ B cells, we tested monoclonal antibodies of this specificity for multireactivity. Two variable region combinations, VH11/V kappa 9 and VH12/V kappa 4, account for greater than 80% of this repertoire, but none of these antibodies exhibited a multireactive phenotype. In contrast, three anti-BrMRBC binding antibodies belonging to the J558 family (BrM1, BrM8, and CH12) showed varying degrees of multireactivity, and bound both highly negatively and positively charged antigens. The amino acid sequences of the VH regions of these antibodies are highly homologous (greater than 85% identical) and they possess large VH-D-J junctions with extensive N-region insertions. The kappa chains of two of these antibodies utilize an identical V kappa gene segment, while the third uses a very different V kappa with only 50% homology. The entire H chain V regions of these antibodies are unusually basic, with isoelectric points of 9.5-10, a feature which might be important in promoting interactions with acidic epitopes. The multireactive antibodies also contain regions with a high concentration of hydroxylside chain amino acids, especially in their VH-D-J junctions. This region also contains acidic amino acid residues, which may be important in binding of positively charged epitopes. We propose that an open, accessible binding site and a charge polarity may be features which facilitate the binding of charged epitopes, providing a structural basis for multireactivity of at least some antibodies.

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Antigen-binding repertoire and Ig H chain gene usage among B cell hybridomas from normal and autoimmune mice.

Cited by 25 publications

References 0 publications

How Specific Should Immunological Memory Be?

How Specific Should Immunological Memory Be?

Posttranslational protein modifications, apoptosis, and the bypass of tolerance to autoantigens

Correlation of antibody multireactivity with variable region primary structure among murine anti‐erythrocyte autoantibodies

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