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By Frank J. Dixon (Ed.)

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Extra resources for Advances in Immunology, Vol. 42

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40 NORMAN R. , 1983; Klinman and Stone, 1983). However, the term “predominant clonotype” applies to a variety of circumstances wherein immunized animals of a given murine strain ultimately produce an antibody population that contains a high representation of a single clonotype or clonotype family. In certain instances, such as B cells of A strain mice bearing the major CRI in response to the ARS haptenic determinant, the representation of B cells of the predominant clonotype in the primary B cell repertoire is quite low (1-3/107 B cells) (Sigal, 1982).

Overall, the proportion of B cell precursors that are responsive in fragment culture appears to be approximately 5% of total bone 36 NORMAN R. KLINMAN AND PHYLLIS-JEAN LINTON marrow cells or 6% of sIg- bone marrow cells. For comparisons to splenic B cells, wherein responsive sIg' cells represent approximately 40% of the total population, a normalization factor of seven has generally been used for comparison of the two cell populations. , 1981), yields a population that is at least 80% responsive in the fragment culture system (Neil and Klinman, 1987).

In toto, the above findings indicate that if tolerance induction plays a significant role in shaping the primary B cell repertoire, the effects of this induction would be highly clonotype dependent. Thus, it would be anticipated that B cells would persist in the mature B cell repertoire that could recognize (1) self-antigens that did not access the developmental milieu within the bone marrow of maturing tolerance susceptible B cells, (2) antigens that did access this milieu but at insufficient concentration to interact sufficiently with the developing B cell population, (3)antigens that are present in sufficient concentration but could not be presented in the multivalent fashion, and (4) antigens recognized by immature precursor cells whose receptor affinity is too low to enable tolerance induction.

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